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Allopurinol extension trial backs treat-to-target approach in gout
In the treatment of gout, dose escalation of allopurinol to achieve target serum urate levels at or below 6 mg/dL appears safe and effective, even among patients with chronic kidney disease, according to a new open-label, extension study. The results build on a 12-month study that had shown safety and efficacy of the strategy.
The new results compared adverse events and serum urate levels between patients who stayed at increased allopurinol doses after achieving target serum urate levels, and control patients who were switched to a strategy of treating to target.
Dr. Stamp did emphasize the need to monitor liver and kidney function, as well as for rashes.
Allopurinol is approved at doses as high as 800 mg/day in the United States, and 900 mg/day in Europe, but most physicians rarely exceed 300 mg/day for fear of side effects. Existing guidelines and recommendations offer different opinions. The European League Against Rheumatism (EULAR) recommends switching to another urate-lowering therapy if the maximum dose adjusted to creatinine clearance (CrCl) isn’t effective, while the American College of Rheumatology recommends gradual dose escalation (DE) beyond CrCl-based doses, even in patients with chronic kidney disease.
The earlier study included 183 patients who had failed to achieve serum urate target levels at CrCl dose, which is intended to avoid allopurinol hypersensitivity syndrome and other potential adverse events. The short-term study results favored the DE approach. At 1 year, there was no difference in adverse events between the 93 control subjects and the 90 DE subjects. The DE group experienced an average serum urate reduction of 1.5 mg/dL, compared with 0.35 mg/dL in the control group (P less than .001). Overall, 32% of controls and 69% of the dose escalation group had achieved serum urate of 6.0 mg/dL or less.
In the extension study, subjects in the control group were switched to a strategy of dose escalation (control/DE), while the patients in the original treatment group remained at their existing allopurinol doses (DE/DE). Those who switched had a mean reduction in serum urate of 1.1 mg/dL, compared with an increase of 0.1 mg/dL in the DE/DE group (P less than .001).
From baseline to month 24, the control/DE group experienced a change in serum urate from 7.13 mg/dL to 5.7 mg/dL, while the DE/DE group experienced a change from 7.18 mg/dL to 5.4 mg/dL.
Both groups had a significant reduction in gout flares, but there was no difference in flare reduction between the two groups at 24 months.
Of those with a tophus at baseline, 6 (16%) of 37 of the control/DE group and 4 (13%) of 31 of the DE/DE group had complete resolution of all tophi between months 12 and 24. Measurable tophi completely resolved between baseline and 24 months in the same percentage of patients (29%) in each group. Tophus size decline significantly overall in both groups together, and there was no difference between the randomized groups.
In the control/DE group, there were 38 serious adverse events in 14 patients, compared with 33 serious adverse events in 22 patients in the DE/DE group. None of the serious adverse events were believed to be related to allopurinol. There were four deaths in the control/DE group and three in the DE/DE group between months 12 and 24, but none of the deaths were believed to be related to allopurinol.
“It is common that people don’t respond to allopurinol at doses based on kidney function and then the dose is not increased. This should give prescribers more confidence to increase the dose,” Dr. Stamp said.
The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
In the treatment of gout, dose escalation of allopurinol to achieve target serum urate levels at or below 6 mg/dL appears safe and effective, even among patients with chronic kidney disease, according to a new open-label, extension study. The results build on a 12-month study that had shown safety and efficacy of the strategy.
The new results compared adverse events and serum urate levels between patients who stayed at increased allopurinol doses after achieving target serum urate levels, and control patients who were switched to a strategy of treating to target.
Dr. Stamp did emphasize the need to monitor liver and kidney function, as well as for rashes.
Allopurinol is approved at doses as high as 800 mg/day in the United States, and 900 mg/day in Europe, but most physicians rarely exceed 300 mg/day for fear of side effects. Existing guidelines and recommendations offer different opinions. The European League Against Rheumatism (EULAR) recommends switching to another urate-lowering therapy if the maximum dose adjusted to creatinine clearance (CrCl) isn’t effective, while the American College of Rheumatology recommends gradual dose escalation (DE) beyond CrCl-based doses, even in patients with chronic kidney disease.
The earlier study included 183 patients who had failed to achieve serum urate target levels at CrCl dose, which is intended to avoid allopurinol hypersensitivity syndrome and other potential adverse events. The short-term study results favored the DE approach. At 1 year, there was no difference in adverse events between the 93 control subjects and the 90 DE subjects. The DE group experienced an average serum urate reduction of 1.5 mg/dL, compared with 0.35 mg/dL in the control group (P less than .001). Overall, 32% of controls and 69% of the dose escalation group had achieved serum urate of 6.0 mg/dL or less.
In the extension study, subjects in the control group were switched to a strategy of dose escalation (control/DE), while the patients in the original treatment group remained at their existing allopurinol doses (DE/DE). Those who switched had a mean reduction in serum urate of 1.1 mg/dL, compared with an increase of 0.1 mg/dL in the DE/DE group (P less than .001).
From baseline to month 24, the control/DE group experienced a change in serum urate from 7.13 mg/dL to 5.7 mg/dL, while the DE/DE group experienced a change from 7.18 mg/dL to 5.4 mg/dL.
Both groups had a significant reduction in gout flares, but there was no difference in flare reduction between the two groups at 24 months.
Of those with a tophus at baseline, 6 (16%) of 37 of the control/DE group and 4 (13%) of 31 of the DE/DE group had complete resolution of all tophi between months 12 and 24. Measurable tophi completely resolved between baseline and 24 months in the same percentage of patients (29%) in each group. Tophus size decline significantly overall in both groups together, and there was no difference between the randomized groups.
In the control/DE group, there were 38 serious adverse events in 14 patients, compared with 33 serious adverse events in 22 patients in the DE/DE group. None of the serious adverse events were believed to be related to allopurinol. There were four deaths in the control/DE group and three in the DE/DE group between months 12 and 24, but none of the deaths were believed to be related to allopurinol.
“It is common that people don’t respond to allopurinol at doses based on kidney function and then the dose is not increased. This should give prescribers more confidence to increase the dose,” Dr. Stamp said.
The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
In the treatment of gout, dose escalation of allopurinol to achieve target serum urate levels at or below 6 mg/dL appears safe and effective, even among patients with chronic kidney disease, according to a new open-label, extension study. The results build on a 12-month study that had shown safety and efficacy of the strategy.
The new results compared adverse events and serum urate levels between patients who stayed at increased allopurinol doses after achieving target serum urate levels, and control patients who were switched to a strategy of treating to target.
Dr. Stamp did emphasize the need to monitor liver and kidney function, as well as for rashes.
Allopurinol is approved at doses as high as 800 mg/day in the United States, and 900 mg/day in Europe, but most physicians rarely exceed 300 mg/day for fear of side effects. Existing guidelines and recommendations offer different opinions. The European League Against Rheumatism (EULAR) recommends switching to another urate-lowering therapy if the maximum dose adjusted to creatinine clearance (CrCl) isn’t effective, while the American College of Rheumatology recommends gradual dose escalation (DE) beyond CrCl-based doses, even in patients with chronic kidney disease.
The earlier study included 183 patients who had failed to achieve serum urate target levels at CrCl dose, which is intended to avoid allopurinol hypersensitivity syndrome and other potential adverse events. The short-term study results favored the DE approach. At 1 year, there was no difference in adverse events between the 93 control subjects and the 90 DE subjects. The DE group experienced an average serum urate reduction of 1.5 mg/dL, compared with 0.35 mg/dL in the control group (P less than .001). Overall, 32% of controls and 69% of the dose escalation group had achieved serum urate of 6.0 mg/dL or less.
In the extension study, subjects in the control group were switched to a strategy of dose escalation (control/DE), while the patients in the original treatment group remained at their existing allopurinol doses (DE/DE). Those who switched had a mean reduction in serum urate of 1.1 mg/dL, compared with an increase of 0.1 mg/dL in the DE/DE group (P less than .001).
From baseline to month 24, the control/DE group experienced a change in serum urate from 7.13 mg/dL to 5.7 mg/dL, while the DE/DE group experienced a change from 7.18 mg/dL to 5.4 mg/dL.
Both groups had a significant reduction in gout flares, but there was no difference in flare reduction between the two groups at 24 months.
Of those with a tophus at baseline, 6 (16%) of 37 of the control/DE group and 4 (13%) of 31 of the DE/DE group had complete resolution of all tophi between months 12 and 24. Measurable tophi completely resolved between baseline and 24 months in the same percentage of patients (29%) in each group. Tophus size decline significantly overall in both groups together, and there was no difference between the randomized groups.
In the control/DE group, there were 38 serious adverse events in 14 patients, compared with 33 serious adverse events in 22 patients in the DE/DE group. None of the serious adverse events were believed to be related to allopurinol. There were four deaths in the control/DE group and three in the DE/DE group between months 12 and 24, but none of the deaths were believed to be related to allopurinol.
“It is common that people don’t respond to allopurinol at doses based on kidney function and then the dose is not increased. This should give prescribers more confidence to increase the dose,” Dr. Stamp said.
The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: An extension study showed continued safety and efficacy of heightened allopurinol doses using a dose-escalation approach.
Major finding: A treat-to-target dosing strategy had a safety profile similar to that of a maximum dose adjusted to creatinine clearance.
Data source: Open-label extension study (n = 183).
Disclosures: The Health Research Council of New Zealand funded the study. Dr. Stamp has received grants from Ardea Biosciences. One coauthor reported receiving grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees from Takeda, Teijin, and Menarini; grants from Fonterra; and personal fees from Pfizer, Crealta, and Cymabay.
FDA approves once-daily treatment for hyperuricemia in gout
The Food and Drug Administration announced Aug. 21 the approval of Duzallo, a once-daily oral treatment for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone.
Duzallo is a fixed-dose combination of lesinurad 200 mg and allopurinol 300 mg that will be marketed by Ironwood Pharmaceuticals. It will also be available in a lesinurad 200 mg plus allopurinol 200 mg dosage.
“With Duzallo, nearly twice as many patients with uncontrolled gout may be able to achieve target serum uric acid levels compared to those patients taking allopurinol alone, which is important, considering the significant unmet need among uncontrolled gout patients to get to goal of under 6 mg/dL,” said Tom McCourt, senior vice president of marketing and sales and chief commercial officer at Ironwood in an announcement from the company.
Duzallo is the first drug that combines the current standard of care for the treatment of hyperuricemia associated with gout, allopurinol, with the most recent FDA-approved treatment for gout, lesinurad (Zurampic). Allopurinol is an xanthine oxidase inhibitor whose action differs from that of uricosuric agents such as lesinurad. Allopurinol reduces the production of uric acid, whereas lesinurad increases renal excretion of uric acid by selectively inhibiting the action of URAT1, the uric acid transporter responsible for the majority of renal uric acid reabsorption.
Duzallo is not recommended for the treatment of asymptomatic hyperuricemia. It has a boxed warning regarding the risk of acute renal failure.
Duzallo is expected to be commercially available early in the fourth quarter of 2017.
The Food and Drug Administration announced Aug. 21 the approval of Duzallo, a once-daily oral treatment for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone.
Duzallo is a fixed-dose combination of lesinurad 200 mg and allopurinol 300 mg that will be marketed by Ironwood Pharmaceuticals. It will also be available in a lesinurad 200 mg plus allopurinol 200 mg dosage.
“With Duzallo, nearly twice as many patients with uncontrolled gout may be able to achieve target serum uric acid levels compared to those patients taking allopurinol alone, which is important, considering the significant unmet need among uncontrolled gout patients to get to goal of under 6 mg/dL,” said Tom McCourt, senior vice president of marketing and sales and chief commercial officer at Ironwood in an announcement from the company.
Duzallo is the first drug that combines the current standard of care for the treatment of hyperuricemia associated with gout, allopurinol, with the most recent FDA-approved treatment for gout, lesinurad (Zurampic). Allopurinol is an xanthine oxidase inhibitor whose action differs from that of uricosuric agents such as lesinurad. Allopurinol reduces the production of uric acid, whereas lesinurad increases renal excretion of uric acid by selectively inhibiting the action of URAT1, the uric acid transporter responsible for the majority of renal uric acid reabsorption.
Duzallo is not recommended for the treatment of asymptomatic hyperuricemia. It has a boxed warning regarding the risk of acute renal failure.
Duzallo is expected to be commercially available early in the fourth quarter of 2017.
The Food and Drug Administration announced Aug. 21 the approval of Duzallo, a once-daily oral treatment for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone.
Duzallo is a fixed-dose combination of lesinurad 200 mg and allopurinol 300 mg that will be marketed by Ironwood Pharmaceuticals. It will also be available in a lesinurad 200 mg plus allopurinol 200 mg dosage.
“With Duzallo, nearly twice as many patients with uncontrolled gout may be able to achieve target serum uric acid levels compared to those patients taking allopurinol alone, which is important, considering the significant unmet need among uncontrolled gout patients to get to goal of under 6 mg/dL,” said Tom McCourt, senior vice president of marketing and sales and chief commercial officer at Ironwood in an announcement from the company.
Duzallo is the first drug that combines the current standard of care for the treatment of hyperuricemia associated with gout, allopurinol, with the most recent FDA-approved treatment for gout, lesinurad (Zurampic). Allopurinol is an xanthine oxidase inhibitor whose action differs from that of uricosuric agents such as lesinurad. Allopurinol reduces the production of uric acid, whereas lesinurad increases renal excretion of uric acid by selectively inhibiting the action of URAT1, the uric acid transporter responsible for the majority of renal uric acid reabsorption.
Duzallo is not recommended for the treatment of asymptomatic hyperuricemia. It has a boxed warning regarding the risk of acute renal failure.
Duzallo is expected to be commercially available early in the fourth quarter of 2017.
Musculoskeletal ultrasound training now offered in nearly all U.S. rheumatology fellowships
Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.
Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.
The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).
While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.
This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.
Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)
Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).
Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.
“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”
While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.
“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”
This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.
The researchers reported no relevant financial disclosures.
[email protected]
On Twitter @eaztweets
Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.
Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.
The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).
While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.
This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.
Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)
Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).
Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.
“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”
While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.
“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”
This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.
The researchers reported no relevant financial disclosures.
[email protected]
On Twitter @eaztweets
Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.
Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.
The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).
While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.
This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.
Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)
Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).
Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.
“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”
While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.
“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”
This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.
The researchers reported no relevant financial disclosures.
[email protected]
On Twitter @eaztweets
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: Of 108 program directors who responded to a survey, 101 (94%) offered a musculoskeletal ultrasound fellowship.
Data source: Survey of 113 rheumatology fellowship program directors gathered from the Fellowship and Residency Electronic Interactive Database Access (FREIDA) online database.
Disclosures: The investigators reported no relevant financial disclosures.
For acute gout, corticosteroids look safer than NSAIDs
For the treatment of acute gout, corticosteroids may be as effective as nonsteroidal anti-inflammatory drugs but with fewer side effects, based on findings from a meta-analysis of six randomized, controlled trials.
“There is insufficient information to determine the comparative efficacy of corticosteroids and NSAID[s] to treat acute gout, while corticosteroids appear to have a more favorable safety profile for selected [adverse events],” Christy A. Billy, MD, of the University of Sydney and her coauthors wrote in their report published online in the Journal of Rheumatology (J Rheumatol. 2017 Aug. doi: 10.3899/jrheum.170137).
Two previous systematic reviews also suggested that corticosteroids may be therapeutically equivalent to but safer than NSAIDs, but both were based on a very small number of available studies and suffered from statistical between-trial heterogeneity.
The meta-analysis of six trials included a total of 817 patients. The trials had a mean follow-up of 15 days. Two trials were in hospitalized patients, two involved patients in the emergency department, one included outpatients, and one did not disclose the location of clinical presentation. Mean age of participants ranged from 44 years to 65.9 years, and the proportion of men ranged from 70% to 100%.
With respect to pain scores, the researchers found no significant difference between corticosteroid and NSAIDs within 7 days of treatment based on moderate-quality evidence from two randomized, controlled trials (RCTs) involving 534 patients (standardized mean difference = –0.09; 95% confidence interval, –0.26 to 0.08). There was also no difference between the two on pain after 7 or more days based on low-quality evidence from two RCTs of 506 patients (SMD = 0.32; 95% CI, –0.27 to 0.92). There was no evidence of statistical heterogeneity in the short-term trials, but there was evidence of significant heterogeneity in trials measuring treatment effects for 7 days or longer (P = .01; I2 [heterogeneity] = 85%).
Two RCTs of 173 patients gave low-quality evidence to show no difference between corticosteroids and NSAIDs in the rate of treatment response in the short term (relative risk, 1.07; 95% CI, 0.80-1.44; moderate heterogeneity, P = .15, I2 = 53%). One long-term study of the rate of treatment response provided similar results. There were also no between-group differences in joint swelling, erythema, tenderness, or activity limitations.
The investigators discovered that patients who took corticosteroids had a lower risk of indigestion in three RCTs with 526 patients (RR, 0.50; 95% CI, 0.27-0.92), nausea in three RCTs of 566 patients (RR, 0.25; 95% CI, 0.11-0.54), and vomiting in two RCTs totaling 506 patients (RR, 0.11; 95% CI, 0.02-0.56).
Patients taking corticosteroids had a higher risk of rash in two RCTs of 506 patients (RR, 4.62; 95% CI, 1.34-15.97). There was statistically significant heterogeneity in summary effects of treatment for total adverse events across all six studies (P = .04; I2 = 56%).
This meta-analysis was limited by the small number of clinical trials available for inclusion, which prevented the estimate of a number of outcomes and subgroup analyses. There was also a high risk of bias in many of the studies. Only half of the studies confirmed the diagnosis of gout by the presence of monosodium urate crystals within joint spaces. No studies reported on the effects of treatment on kidney function or injury.
The authors disclosed no source of funding or financial relationships.
For the treatment of acute gout, corticosteroids may be as effective as nonsteroidal anti-inflammatory drugs but with fewer side effects, based on findings from a meta-analysis of six randomized, controlled trials.
“There is insufficient information to determine the comparative efficacy of corticosteroids and NSAID[s] to treat acute gout, while corticosteroids appear to have a more favorable safety profile for selected [adverse events],” Christy A. Billy, MD, of the University of Sydney and her coauthors wrote in their report published online in the Journal of Rheumatology (J Rheumatol. 2017 Aug. doi: 10.3899/jrheum.170137).
Two previous systematic reviews also suggested that corticosteroids may be therapeutically equivalent to but safer than NSAIDs, but both were based on a very small number of available studies and suffered from statistical between-trial heterogeneity.
The meta-analysis of six trials included a total of 817 patients. The trials had a mean follow-up of 15 days. Two trials were in hospitalized patients, two involved patients in the emergency department, one included outpatients, and one did not disclose the location of clinical presentation. Mean age of participants ranged from 44 years to 65.9 years, and the proportion of men ranged from 70% to 100%.
With respect to pain scores, the researchers found no significant difference between corticosteroid and NSAIDs within 7 days of treatment based on moderate-quality evidence from two randomized, controlled trials (RCTs) involving 534 patients (standardized mean difference = –0.09; 95% confidence interval, –0.26 to 0.08). There was also no difference between the two on pain after 7 or more days based on low-quality evidence from two RCTs of 506 patients (SMD = 0.32; 95% CI, –0.27 to 0.92). There was no evidence of statistical heterogeneity in the short-term trials, but there was evidence of significant heterogeneity in trials measuring treatment effects for 7 days or longer (P = .01; I2 [heterogeneity] = 85%).
Two RCTs of 173 patients gave low-quality evidence to show no difference between corticosteroids and NSAIDs in the rate of treatment response in the short term (relative risk, 1.07; 95% CI, 0.80-1.44; moderate heterogeneity, P = .15, I2 = 53%). One long-term study of the rate of treatment response provided similar results. There were also no between-group differences in joint swelling, erythema, tenderness, or activity limitations.
The investigators discovered that patients who took corticosteroids had a lower risk of indigestion in three RCTs with 526 patients (RR, 0.50; 95% CI, 0.27-0.92), nausea in three RCTs of 566 patients (RR, 0.25; 95% CI, 0.11-0.54), and vomiting in two RCTs totaling 506 patients (RR, 0.11; 95% CI, 0.02-0.56).
Patients taking corticosteroids had a higher risk of rash in two RCTs of 506 patients (RR, 4.62; 95% CI, 1.34-15.97). There was statistically significant heterogeneity in summary effects of treatment for total adverse events across all six studies (P = .04; I2 = 56%).
This meta-analysis was limited by the small number of clinical trials available for inclusion, which prevented the estimate of a number of outcomes and subgroup analyses. There was also a high risk of bias in many of the studies. Only half of the studies confirmed the diagnosis of gout by the presence of monosodium urate crystals within joint spaces. No studies reported on the effects of treatment on kidney function or injury.
The authors disclosed no source of funding or financial relationships.
For the treatment of acute gout, corticosteroids may be as effective as nonsteroidal anti-inflammatory drugs but with fewer side effects, based on findings from a meta-analysis of six randomized, controlled trials.
“There is insufficient information to determine the comparative efficacy of corticosteroids and NSAID[s] to treat acute gout, while corticosteroids appear to have a more favorable safety profile for selected [adverse events],” Christy A. Billy, MD, of the University of Sydney and her coauthors wrote in their report published online in the Journal of Rheumatology (J Rheumatol. 2017 Aug. doi: 10.3899/jrheum.170137).
Two previous systematic reviews also suggested that corticosteroids may be therapeutically equivalent to but safer than NSAIDs, but both were based on a very small number of available studies and suffered from statistical between-trial heterogeneity.
The meta-analysis of six trials included a total of 817 patients. The trials had a mean follow-up of 15 days. Two trials were in hospitalized patients, two involved patients in the emergency department, one included outpatients, and one did not disclose the location of clinical presentation. Mean age of participants ranged from 44 years to 65.9 years, and the proportion of men ranged from 70% to 100%.
With respect to pain scores, the researchers found no significant difference between corticosteroid and NSAIDs within 7 days of treatment based on moderate-quality evidence from two randomized, controlled trials (RCTs) involving 534 patients (standardized mean difference = –0.09; 95% confidence interval, –0.26 to 0.08). There was also no difference between the two on pain after 7 or more days based on low-quality evidence from two RCTs of 506 patients (SMD = 0.32; 95% CI, –0.27 to 0.92). There was no evidence of statistical heterogeneity in the short-term trials, but there was evidence of significant heterogeneity in trials measuring treatment effects for 7 days or longer (P = .01; I2 [heterogeneity] = 85%).
Two RCTs of 173 patients gave low-quality evidence to show no difference between corticosteroids and NSAIDs in the rate of treatment response in the short term (relative risk, 1.07; 95% CI, 0.80-1.44; moderate heterogeneity, P = .15, I2 = 53%). One long-term study of the rate of treatment response provided similar results. There were also no between-group differences in joint swelling, erythema, tenderness, or activity limitations.
The investigators discovered that patients who took corticosteroids had a lower risk of indigestion in three RCTs with 526 patients (RR, 0.50; 95% CI, 0.27-0.92), nausea in three RCTs of 566 patients (RR, 0.25; 95% CI, 0.11-0.54), and vomiting in two RCTs totaling 506 patients (RR, 0.11; 95% CI, 0.02-0.56).
Patients taking corticosteroids had a higher risk of rash in two RCTs of 506 patients (RR, 4.62; 95% CI, 1.34-15.97). There was statistically significant heterogeneity in summary effects of treatment for total adverse events across all six studies (P = .04; I2 = 56%).
This meta-analysis was limited by the small number of clinical trials available for inclusion, which prevented the estimate of a number of outcomes and subgroup analyses. There was also a high risk of bias in many of the studies. Only half of the studies confirmed the diagnosis of gout by the presence of monosodium urate crystals within joint spaces. No studies reported on the effects of treatment on kidney function or injury.
The authors disclosed no source of funding or financial relationships.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point: Corticosteroids had a similar efficacy but a better safety profile than NSAIDs.
Major finding: Corticosteroids had efficacy similar to NSAIDs in the treatment of acute gout.
Data source: Meta-analysis of six randomized, controlled trials (n = 817).
Disclosures: The authors disclosed no source of funding or financial relationships.
Allopurinol and ventricular arrhythmias: Is there a link?
MADRID – Newly begun allopurinol treatment of elderly patients was linked with a significantly reduced incidence of ventricular arrhythmias in a review of more than 28,000 Medicare beneficiaries.
The antiarrhythmic effect appeared to strengthen with more prolonged allopurinol treatment, reaching a 28% reduction in ventricular arrhythmia incidence among patients on allopurinol for more than 2 years, compared with patients who never received the uric acid reducer, Jasvinder A. Singh, MD, reported in a poster at the European Congress of Rheumatology.
He and his associates used data collected from more than 3 million U.S. Medicare beneficiaries during 2006-2012 from a random Medicare 5% sample. This group included 28,755 patients who began a prescription for allopurinol after not having filled a prescription for the drug during the prior 365 days. The patients averaged 77 years of age.
The outcome of interest was a new onset ventricular arrhythmia, defined as an arrhythmia episode in a patient with no prior record of arrhythmia during the previous 365 days. Arrhythmia occurred in 2,538 of the patients on new allopurinol treatment (9%).
In a multivariate analysis that compared new allopurinol users with patients without allopurinol exposure and controlled for several demographic and clinical features, allopurinol use was linked with a statistically significant 18% reduced rate of incident ventricular arrhythmias in those who recieved it, compared with similar patients who did not receive allopurinol, Dr. Singh and his associates reported.
An additional analysis looked at the relative risk reduction associated with various lengths of allopurinol use. Compared with patients not on allopurinol, those taking it for more than 2 years had a significant 28% reduced rate of arrhythmias; those on it for 6 months to 2 years had a significant 24% reduction in incident arrhythmias; and those on it for 1-180 days had no significant change in their arrhythmia incidence.
Other individual factors that significantly correlated with increased ventricular arrhythmias included older age, male sex, African American race, presence of comorbidities, and treatment with a beta-blockers. Like allopurinol, treatment with a statin linked with a significantly reduced arrhythmia incidence.
In a second, related report at the meeting, Dr. Singh and his associates used a very similar data set to see if a link existed between new-onset allopurinol treatment and a reduced incidence of peripheral artery disease. This analysis showed that allopurinol use linked with a statistically significant 12% reduction in new onset peripheral artery disease. They again found that the clinical impact of allopurinol treatment grew larger as the duration of allopurinol treatment increased.
Dr. Singh has financial ties to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda.
[email protected]
On Twitter @mitchelzoler
MADRID – Newly begun allopurinol treatment of elderly patients was linked with a significantly reduced incidence of ventricular arrhythmias in a review of more than 28,000 Medicare beneficiaries.
The antiarrhythmic effect appeared to strengthen with more prolonged allopurinol treatment, reaching a 28% reduction in ventricular arrhythmia incidence among patients on allopurinol for more than 2 years, compared with patients who never received the uric acid reducer, Jasvinder A. Singh, MD, reported in a poster at the European Congress of Rheumatology.
He and his associates used data collected from more than 3 million U.S. Medicare beneficiaries during 2006-2012 from a random Medicare 5% sample. This group included 28,755 patients who began a prescription for allopurinol after not having filled a prescription for the drug during the prior 365 days. The patients averaged 77 years of age.
The outcome of interest was a new onset ventricular arrhythmia, defined as an arrhythmia episode in a patient with no prior record of arrhythmia during the previous 365 days. Arrhythmia occurred in 2,538 of the patients on new allopurinol treatment (9%).
In a multivariate analysis that compared new allopurinol users with patients without allopurinol exposure and controlled for several demographic and clinical features, allopurinol use was linked with a statistically significant 18% reduced rate of incident ventricular arrhythmias in those who recieved it, compared with similar patients who did not receive allopurinol, Dr. Singh and his associates reported.
An additional analysis looked at the relative risk reduction associated with various lengths of allopurinol use. Compared with patients not on allopurinol, those taking it for more than 2 years had a significant 28% reduced rate of arrhythmias; those on it for 6 months to 2 years had a significant 24% reduction in incident arrhythmias; and those on it for 1-180 days had no significant change in their arrhythmia incidence.
Other individual factors that significantly correlated with increased ventricular arrhythmias included older age, male sex, African American race, presence of comorbidities, and treatment with a beta-blockers. Like allopurinol, treatment with a statin linked with a significantly reduced arrhythmia incidence.
In a second, related report at the meeting, Dr. Singh and his associates used a very similar data set to see if a link existed between new-onset allopurinol treatment and a reduced incidence of peripheral artery disease. This analysis showed that allopurinol use linked with a statistically significant 12% reduction in new onset peripheral artery disease. They again found that the clinical impact of allopurinol treatment grew larger as the duration of allopurinol treatment increased.
Dr. Singh has financial ties to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda.
[email protected]
On Twitter @mitchelzoler
MADRID – Newly begun allopurinol treatment of elderly patients was linked with a significantly reduced incidence of ventricular arrhythmias in a review of more than 28,000 Medicare beneficiaries.
The antiarrhythmic effect appeared to strengthen with more prolonged allopurinol treatment, reaching a 28% reduction in ventricular arrhythmia incidence among patients on allopurinol for more than 2 years, compared with patients who never received the uric acid reducer, Jasvinder A. Singh, MD, reported in a poster at the European Congress of Rheumatology.
He and his associates used data collected from more than 3 million U.S. Medicare beneficiaries during 2006-2012 from a random Medicare 5% sample. This group included 28,755 patients who began a prescription for allopurinol after not having filled a prescription for the drug during the prior 365 days. The patients averaged 77 years of age.
The outcome of interest was a new onset ventricular arrhythmia, defined as an arrhythmia episode in a patient with no prior record of arrhythmia during the previous 365 days. Arrhythmia occurred in 2,538 of the patients on new allopurinol treatment (9%).
In a multivariate analysis that compared new allopurinol users with patients without allopurinol exposure and controlled for several demographic and clinical features, allopurinol use was linked with a statistically significant 18% reduced rate of incident ventricular arrhythmias in those who recieved it, compared with similar patients who did not receive allopurinol, Dr. Singh and his associates reported.
An additional analysis looked at the relative risk reduction associated with various lengths of allopurinol use. Compared with patients not on allopurinol, those taking it for more than 2 years had a significant 28% reduced rate of arrhythmias; those on it for 6 months to 2 years had a significant 24% reduction in incident arrhythmias; and those on it for 1-180 days had no significant change in their arrhythmia incidence.
Other individual factors that significantly correlated with increased ventricular arrhythmias included older age, male sex, African American race, presence of comorbidities, and treatment with a beta-blockers. Like allopurinol, treatment with a statin linked with a significantly reduced arrhythmia incidence.
In a second, related report at the meeting, Dr. Singh and his associates used a very similar data set to see if a link existed between new-onset allopurinol treatment and a reduced incidence of peripheral artery disease. This analysis showed that allopurinol use linked with a statistically significant 12% reduction in new onset peripheral artery disease. They again found that the clinical impact of allopurinol treatment grew larger as the duration of allopurinol treatment increased.
Dr. Singh has financial ties to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda.
[email protected]
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Patients on allopurinol for more than 2 years had a 28% reduced rate of ventricular arrhythmias, compared with those not on allopurinol treatment.
Data source: A 5% random sample of Medicare beneficiaries during 2006-2012.
Disclosures: Dr. Singh has been a consultant to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda and has received research support from Savient and Takeda.
Trial supports naproxen over low-dose colchicine for acute gout
BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.
“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.
The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.
CONTACT was a multicenter, randomized, open-label trial involving 399 patients recruited at 100 primary care practices. Participants were mostly men (87%) and had a mean age of 59 years.
“The eligibility criteria were designed to reflect the pragmatic nature of the trial, but also to enable us to recruit the sorts of patients in whom either treatment option would be appropriate in routine practice,” Dr. Roddy explained.
Patients were eligible for inclusion if they had consulted a general practitioner for gout in the preceding 2 years and had a recent attack of acute gout that had been clinically assessed. Patients with medical or other contraindications to using either drug were excluded.
After giving their informed consent and completing a baseline questionnaire, patients were randomized to receive either naproxen as a single 750-mg dose, then as 250 mg three times a day for a maximum of 7 days, which is the licensed dose for gout in the United Kingdom, or 500 mcg of colchicine three times a day for 4 days. Patients completed a daily diary for 1 week, noting any pain, side effects, and analgesic drug use and then completed a follow-up questionnaire 4 weeks later.
The primary outcome was the worst pain intensity experienced in the preceding 24 hours, assessed on days 1-7 with a 10-point numeric rating scale (where 10 was the worst pain experienced).
The results showed that pain was reduced to a similar extent in both groups, with a mean difference in pain score between the treatments of 0.20 (95% confidence interval, –0.60 to 0.20) at 7 days and 0.08 (95% CI, –0.54 to 0.39) at 4 weeks’ follow-up, after adjustment for patients’ age, sex, and individual pain scores at baseline.
Greater mean improvement in pain intensity was seen with naproxen than colchicine on the second day of treatment, with a mean difference in pain scores between the groups of 0.48 (95% CI, –0.86 to –0.09) but not on any other day.
During the first 7 days of the study, diarrhea was the most commonly reported side effect occurring in the low-dose colchicine arm, reported by 43.2% of patients vs. 18.0% of those treated with naproxen (adjusted odds ratio, 3.04; 95% CI, 1.75-5.27). Conversely, constipation was a less frequently reported side effect occurring in 4.8% and 18.7% of patients, respectively (OR, 0.20; 95% CI, 0.08-0.49).
Patients treated with low-dose colchicine were also more likely than those treated with naproxen to report headache during the first 7 days (20.5% vs. 10.7%; OR, 1.90; 95% CI, 1.01-3.58).
There were no deaths in the study, and the three serious adverse events that occurred were thought to be unrelated to the study treatment. One NSAID-treated patient developed hospital-acquired pneumonia after elective heart valve surgery, and another NSAID-treated patient had noncardiac chest pain needing hospital treatment. One patient in the colchicine arm developed osteomyelitis that required hospitalization, but it was later thought that the patient might not have had gout to start with.
Between days 1 and 7 of the study, patients treated with low-dose colchicine were more likely to use other analgesic medications than were those treated with naproxen. This included the use of acetaminophen (23.6% vs. 13.4%; adjusted OR, 2.04; 95% CI, 1.10-3.78) and codeine (14.6% vs. 4.7%; aOR, 3.38; 95% CI, 1.45-7.91).
Patients in the low-dose colchicine group were also more likely to use an NSAID other than naproxen at week 4 than were those in the naproxen arm (24.0% vs. 13.4%; aOR, 1.93; 95% CI, 1.05-3.55).
Other secondary endpoints assessed showed no significant difference between the treatments, including changes in global assessment of response, acute gout recurrence, number of health care consultations, and ability to work.
The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.
It’s not surprising that a relatively high dose of an NSAID like naproxen worked well for acute gout in the CONTACT study. That has been shown for multiple NSAIDs, although the quality of that evidence has been questioned (Cochrane Database Syst Rev. 2014 Sep 16;[9]:CD010120). What’s surprising is that colchicine did so well. It would have been informative to include the percentage of patients that responded to each treatment based on a predefined criterion, such as a 50% or greater reduction in pain scores at a given time point. The total colchicine dose used is on the high end of the “low dose” protocols, at 6.0 mg over 4 days, identical to the maximum low-dose over 4 days using current U.S. guidelines (Arthritis Care Res. 2012;64:1447-61). The higher dose may account for its efficacy, but also undoubtedly contributed to the high diarrhea rate of 43% (Arthritis Rheum. 2010;62:1060-8).
Christopher M. Burns, MD, is a rheumatologist at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He has no relevant disclosures.
It’s not surprising that a relatively high dose of an NSAID like naproxen worked well for acute gout in the CONTACT study. That has been shown for multiple NSAIDs, although the quality of that evidence has been questioned (Cochrane Database Syst Rev. 2014 Sep 16;[9]:CD010120). What’s surprising is that colchicine did so well. It would have been informative to include the percentage of patients that responded to each treatment based on a predefined criterion, such as a 50% or greater reduction in pain scores at a given time point. The total colchicine dose used is on the high end of the “low dose” protocols, at 6.0 mg over 4 days, identical to the maximum low-dose over 4 days using current U.S. guidelines (Arthritis Care Res. 2012;64:1447-61). The higher dose may account for its efficacy, but also undoubtedly contributed to the high diarrhea rate of 43% (Arthritis Rheum. 2010;62:1060-8).
Christopher M. Burns, MD, is a rheumatologist at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He has no relevant disclosures.
It’s not surprising that a relatively high dose of an NSAID like naproxen worked well for acute gout in the CONTACT study. That has been shown for multiple NSAIDs, although the quality of that evidence has been questioned (Cochrane Database Syst Rev. 2014 Sep 16;[9]:CD010120). What’s surprising is that colchicine did so well. It would have been informative to include the percentage of patients that responded to each treatment based on a predefined criterion, such as a 50% or greater reduction in pain scores at a given time point. The total colchicine dose used is on the high end of the “low dose” protocols, at 6.0 mg over 4 days, identical to the maximum low-dose over 4 days using current U.S. guidelines (Arthritis Care Res. 2012;64:1447-61). The higher dose may account for its efficacy, but also undoubtedly contributed to the high diarrhea rate of 43% (Arthritis Rheum. 2010;62:1060-8).
Christopher M. Burns, MD, is a rheumatologist at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He has no relevant disclosures.
BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.
“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.
The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.
CONTACT was a multicenter, randomized, open-label trial involving 399 patients recruited at 100 primary care practices. Participants were mostly men (87%) and had a mean age of 59 years.
“The eligibility criteria were designed to reflect the pragmatic nature of the trial, but also to enable us to recruit the sorts of patients in whom either treatment option would be appropriate in routine practice,” Dr. Roddy explained.
Patients were eligible for inclusion if they had consulted a general practitioner for gout in the preceding 2 years and had a recent attack of acute gout that had been clinically assessed. Patients with medical or other contraindications to using either drug were excluded.
After giving their informed consent and completing a baseline questionnaire, patients were randomized to receive either naproxen as a single 750-mg dose, then as 250 mg three times a day for a maximum of 7 days, which is the licensed dose for gout in the United Kingdom, or 500 mcg of colchicine three times a day for 4 days. Patients completed a daily diary for 1 week, noting any pain, side effects, and analgesic drug use and then completed a follow-up questionnaire 4 weeks later.
The primary outcome was the worst pain intensity experienced in the preceding 24 hours, assessed on days 1-7 with a 10-point numeric rating scale (where 10 was the worst pain experienced).
The results showed that pain was reduced to a similar extent in both groups, with a mean difference in pain score between the treatments of 0.20 (95% confidence interval, –0.60 to 0.20) at 7 days and 0.08 (95% CI, –0.54 to 0.39) at 4 weeks’ follow-up, after adjustment for patients’ age, sex, and individual pain scores at baseline.
Greater mean improvement in pain intensity was seen with naproxen than colchicine on the second day of treatment, with a mean difference in pain scores between the groups of 0.48 (95% CI, –0.86 to –0.09) but not on any other day.
During the first 7 days of the study, diarrhea was the most commonly reported side effect occurring in the low-dose colchicine arm, reported by 43.2% of patients vs. 18.0% of those treated with naproxen (adjusted odds ratio, 3.04; 95% CI, 1.75-5.27). Conversely, constipation was a less frequently reported side effect occurring in 4.8% and 18.7% of patients, respectively (OR, 0.20; 95% CI, 0.08-0.49).
Patients treated with low-dose colchicine were also more likely than those treated with naproxen to report headache during the first 7 days (20.5% vs. 10.7%; OR, 1.90; 95% CI, 1.01-3.58).
There were no deaths in the study, and the three serious adverse events that occurred were thought to be unrelated to the study treatment. One NSAID-treated patient developed hospital-acquired pneumonia after elective heart valve surgery, and another NSAID-treated patient had noncardiac chest pain needing hospital treatment. One patient in the colchicine arm developed osteomyelitis that required hospitalization, but it was later thought that the patient might not have had gout to start with.
Between days 1 and 7 of the study, patients treated with low-dose colchicine were more likely to use other analgesic medications than were those treated with naproxen. This included the use of acetaminophen (23.6% vs. 13.4%; adjusted OR, 2.04; 95% CI, 1.10-3.78) and codeine (14.6% vs. 4.7%; aOR, 3.38; 95% CI, 1.45-7.91).
Patients in the low-dose colchicine group were also more likely to use an NSAID other than naproxen at week 4 than were those in the naproxen arm (24.0% vs. 13.4%; aOR, 1.93; 95% CI, 1.05-3.55).
Other secondary endpoints assessed showed no significant difference between the treatments, including changes in global assessment of response, acute gout recurrence, number of health care consultations, and ability to work.
The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.
BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.
“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.
The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.
CONTACT was a multicenter, randomized, open-label trial involving 399 patients recruited at 100 primary care practices. Participants were mostly men (87%) and had a mean age of 59 years.
“The eligibility criteria were designed to reflect the pragmatic nature of the trial, but also to enable us to recruit the sorts of patients in whom either treatment option would be appropriate in routine practice,” Dr. Roddy explained.
Patients were eligible for inclusion if they had consulted a general practitioner for gout in the preceding 2 years and had a recent attack of acute gout that had been clinically assessed. Patients with medical or other contraindications to using either drug were excluded.
After giving their informed consent and completing a baseline questionnaire, patients were randomized to receive either naproxen as a single 750-mg dose, then as 250 mg three times a day for a maximum of 7 days, which is the licensed dose for gout in the United Kingdom, or 500 mcg of colchicine three times a day for 4 days. Patients completed a daily diary for 1 week, noting any pain, side effects, and analgesic drug use and then completed a follow-up questionnaire 4 weeks later.
The primary outcome was the worst pain intensity experienced in the preceding 24 hours, assessed on days 1-7 with a 10-point numeric rating scale (where 10 was the worst pain experienced).
The results showed that pain was reduced to a similar extent in both groups, with a mean difference in pain score between the treatments of 0.20 (95% confidence interval, –0.60 to 0.20) at 7 days and 0.08 (95% CI, –0.54 to 0.39) at 4 weeks’ follow-up, after adjustment for patients’ age, sex, and individual pain scores at baseline.
Greater mean improvement in pain intensity was seen with naproxen than colchicine on the second day of treatment, with a mean difference in pain scores between the groups of 0.48 (95% CI, –0.86 to –0.09) but not on any other day.
During the first 7 days of the study, diarrhea was the most commonly reported side effect occurring in the low-dose colchicine arm, reported by 43.2% of patients vs. 18.0% of those treated with naproxen (adjusted odds ratio, 3.04; 95% CI, 1.75-5.27). Conversely, constipation was a less frequently reported side effect occurring in 4.8% and 18.7% of patients, respectively (OR, 0.20; 95% CI, 0.08-0.49).
Patients treated with low-dose colchicine were also more likely than those treated with naproxen to report headache during the first 7 days (20.5% vs. 10.7%; OR, 1.90; 95% CI, 1.01-3.58).
There were no deaths in the study, and the three serious adverse events that occurred were thought to be unrelated to the study treatment. One NSAID-treated patient developed hospital-acquired pneumonia after elective heart valve surgery, and another NSAID-treated patient had noncardiac chest pain needing hospital treatment. One patient in the colchicine arm developed osteomyelitis that required hospitalization, but it was later thought that the patient might not have had gout to start with.
Between days 1 and 7 of the study, patients treated with low-dose colchicine were more likely to use other analgesic medications than were those treated with naproxen. This included the use of acetaminophen (23.6% vs. 13.4%; adjusted OR, 2.04; 95% CI, 1.10-3.78) and codeine (14.6% vs. 4.7%; aOR, 3.38; 95% CI, 1.45-7.91).
Patients in the low-dose colchicine group were also more likely to use an NSAID other than naproxen at week 4 than were those in the naproxen arm (24.0% vs. 13.4%; aOR, 1.93; 95% CI, 1.05-3.55).
Other secondary endpoints assessed showed no significant difference between the treatments, including changes in global assessment of response, acute gout recurrence, number of health care consultations, and ability to work.
The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.
Key clinical point:
Major finding: The mean difference in pain score between the treatments was 0.20 (95% CI, –0.60 to 0.20) at 7 days, but there was greater mean improvement in pain intensity on day 2 with naproxen.
Data source: The Colchicine or Naproxen Treatment for Acute Gout trial, a randomized, multicenter, open-label trial involving 399 patients with acute gout.
Disclosures: The study was funded by the National Institute for Health Research School for Primary Care Research. Dr. Roddy had no conflicts of interest.
Compounding rules challenge practice norms
As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.
In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.
In the same position statement on compounding, the ACR said it also seeks a change to a Food and Drug Administration rule limiting practitioners’ access to quinacrine, a drug only available through compounding pharmacies that is sometimes used to treat lupus patients. Quinacrine is not on the FDA’s current list of bulk substances approved for compounding, except by special permission. The ACR has asked the agency to add quinacrine to the list, but no one knows when this will happen.
Rheumatologists may also be more restricted than before in terms of which compounding pharmacies they can turn to, as new federal standards divide them into two types – those that can provide medicines in larger quantities and those that can’t.
Steroid fiasco sparked rule revisions
The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.
More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.
The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.
As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.
“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.
“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.
In-office mixing a top concern
Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.
Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.
Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.
Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”
USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.
“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.
“There’s that law of unintended consequences where you snare things in a net that you really don’t want to,” Dr. Huffstutter said.
Marcus Snow, MD, a rheumatologist at the University of Nebraska, Omaha, who also worked on the statement, said that most rheumatologists are likely unaware that their ability to mix drugs in-office has been called into question.
“I brought it up at our division meeting with a group of 10 rheumatologists, and no one was aware that this was coming down the pike,” Dr. Snow said in an interview.
Pediatric issues
Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.
They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.
“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.
Steroid injections can mean avoiding or delaying systemic treatment in children with oligoarticular arthritis, he said. “Most of us consider them a first-line therapy. The hope is that you can get by without having to use meds like methotrexate if you can get a prolonged response in the one or two joints that are active in that patient.”
But Dr. Reinhardt said that, while he mixed his own injections during his fellowship training, Children’s of Omaha now insists that they be prepared by in-house pharmacists, working under sterile hoods. The delay to receiving them in the clinic or procedure room is 40 minutes to an hour, he said, which the clinicians accommodate through careful scheduling.
The change from mixing in-clinic to relying on the central pharmacy came about in recent years, Dr. Reinhardt said, because of broader concerns related to medication storage in the clinics. While ordering from the central pharmacy works for his practice, he said, “I probably only inject maybe 50-70 joints a year, while adult rheumatologists are injecting far more than that. For a busy private practice, I can see that being a huge time constraint,” he said.
Relevance of rules
None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.
Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.
Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”
Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.
Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.
He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.
But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.
The quinacrine problem
A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.
“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”
Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”
Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.
While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.
Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.
Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.
As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.
In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.
In the same position statement on compounding, the ACR said it also seeks a change to a Food and Drug Administration rule limiting practitioners’ access to quinacrine, a drug only available through compounding pharmacies that is sometimes used to treat lupus patients. Quinacrine is not on the FDA’s current list of bulk substances approved for compounding, except by special permission. The ACR has asked the agency to add quinacrine to the list, but no one knows when this will happen.
Rheumatologists may also be more restricted than before in terms of which compounding pharmacies they can turn to, as new federal standards divide them into two types – those that can provide medicines in larger quantities and those that can’t.
Steroid fiasco sparked rule revisions
The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.
More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.
The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.
As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.
“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.
“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.
In-office mixing a top concern
Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.
Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.
Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.
Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”
USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.
“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.
“There’s that law of unintended consequences where you snare things in a net that you really don’t want to,” Dr. Huffstutter said.
Marcus Snow, MD, a rheumatologist at the University of Nebraska, Omaha, who also worked on the statement, said that most rheumatologists are likely unaware that their ability to mix drugs in-office has been called into question.
“I brought it up at our division meeting with a group of 10 rheumatologists, and no one was aware that this was coming down the pike,” Dr. Snow said in an interview.
Pediatric issues
Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.
They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.
“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.
Steroid injections can mean avoiding or delaying systemic treatment in children with oligoarticular arthritis, he said. “Most of us consider them a first-line therapy. The hope is that you can get by without having to use meds like methotrexate if you can get a prolonged response in the one or two joints that are active in that patient.”
But Dr. Reinhardt said that, while he mixed his own injections during his fellowship training, Children’s of Omaha now insists that they be prepared by in-house pharmacists, working under sterile hoods. The delay to receiving them in the clinic or procedure room is 40 minutes to an hour, he said, which the clinicians accommodate through careful scheduling.
The change from mixing in-clinic to relying on the central pharmacy came about in recent years, Dr. Reinhardt said, because of broader concerns related to medication storage in the clinics. While ordering from the central pharmacy works for his practice, he said, “I probably only inject maybe 50-70 joints a year, while adult rheumatologists are injecting far more than that. For a busy private practice, I can see that being a huge time constraint,” he said.
Relevance of rules
None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.
Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.
Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”
Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.
Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.
He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.
But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.
The quinacrine problem
A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.
“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”
Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”
Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.
While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.
Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.
Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.
As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.
In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.
In the same position statement on compounding, the ACR said it also seeks a change to a Food and Drug Administration rule limiting practitioners’ access to quinacrine, a drug only available through compounding pharmacies that is sometimes used to treat lupus patients. Quinacrine is not on the FDA’s current list of bulk substances approved for compounding, except by special permission. The ACR has asked the agency to add quinacrine to the list, but no one knows when this will happen.
Rheumatologists may also be more restricted than before in terms of which compounding pharmacies they can turn to, as new federal standards divide them into two types – those that can provide medicines in larger quantities and those that can’t.
Steroid fiasco sparked rule revisions
The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.
More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.
The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.
As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.
“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.
“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.
In-office mixing a top concern
Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.
Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.
Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.
Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”
USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.
“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.
“There’s that law of unintended consequences where you snare things in a net that you really don’t want to,” Dr. Huffstutter said.
Marcus Snow, MD, a rheumatologist at the University of Nebraska, Omaha, who also worked on the statement, said that most rheumatologists are likely unaware that their ability to mix drugs in-office has been called into question.
“I brought it up at our division meeting with a group of 10 rheumatologists, and no one was aware that this was coming down the pike,” Dr. Snow said in an interview.
Pediatric issues
Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.
They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.
“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.
Steroid injections can mean avoiding or delaying systemic treatment in children with oligoarticular arthritis, he said. “Most of us consider them a first-line therapy. The hope is that you can get by without having to use meds like methotrexate if you can get a prolonged response in the one or two joints that are active in that patient.”
But Dr. Reinhardt said that, while he mixed his own injections during his fellowship training, Children’s of Omaha now insists that they be prepared by in-house pharmacists, working under sterile hoods. The delay to receiving them in the clinic or procedure room is 40 minutes to an hour, he said, which the clinicians accommodate through careful scheduling.
The change from mixing in-clinic to relying on the central pharmacy came about in recent years, Dr. Reinhardt said, because of broader concerns related to medication storage in the clinics. While ordering from the central pharmacy works for his practice, he said, “I probably only inject maybe 50-70 joints a year, while adult rheumatologists are injecting far more than that. For a busy private practice, I can see that being a huge time constraint,” he said.
Relevance of rules
None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.
Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.
Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”
Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.
Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.
He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.
But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.
The quinacrine problem
A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.
“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”
Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”
Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.
While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.
Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.
Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.
First treat-to-target gout trial supports allopurinol dose escalation
Gradual dose escalation of allopurinol achieved target serum urate levels without causing excess adverse effects in patients with gout who tolerated but responded inadequately to creatinine clearance–based dosing, including in patients with chronic kidney disease, investigators reported in Annals of the Rheumatic Diseases.
The study is the first randomized, controlled trial to examine treat-to-target allopurinol dose escalation in gout. “We believe this approach can be undertaken in all patients who tolerate allopurinol,” lead investigator Lisa Stamp, MD, said in an interview. However, it is important to monitor kidney and liver function.”
To help settle these debates, Dr. Stamp and her associates recruited 183 patients with gout whose serum urate levels averaged 7.15 mg/dL (standard deviation, 1.6 mg/dL) despite at least 1 month of at least a creatinine clearance–based allopurinol dose (average, 269 mg/day). For the next 12 months, patients either continued this dose or increased it monthly until serum urate fell below 6 mg/dL (Ann Rheum Dis. 2017 March 17. doi: 10.1136/annrheumdis-2016-210872).
At month 12, 69% of dose-escalation patients and 32% of controls reached this target (P less than .001; odds ratio, 4.3; 95% confidence interval, 2.4-7.9). Serum urate levels dropped by a mean of 1.5 mg/dL with dose escalation and by 0.34 mg/dL in controls (P less than .001). Thus, dose escalation cut serum urate levels by an additional 1.2 mg/dL (95% CI, 0.67-1.5 mg/dL; P less than .001). The average final daily allopurinol dose was 413 mg (range, 0-900 mg) with dose escalation and 288 mg (0-600 mg) for controls.
Notably, renal function measures did not differ between arms. “There has been long-standing concern about whether it is safe to escalate allopurinol doses in persons with chronic kidney disease,” said Kenneth Saag, MD, of the University of Alabama at Birmingham, who was not involved in the trial. “This study contributes to the limited literature supporting the practice of treating to serum urate targets, even in patients with underlying kidney disease.”
Fully 52% of trial participants had chronic kidney disease, and 44% had tophi. “Thus, our population is representative of people with gout, represents real-life clinical practice, and the results are generalizable to other gout populations,” the investigators wrote.
The findings support the ACR recommendation to gradually titrate urate-lowering therapy while performing close laboratory monitoring, said Tuhina Neogi, MD, of Boston University, who was not involved in the study. This approach is “efficacious and relatively safe for patients who have already tolerated lower doses of allopurinol, but have not yet achieved their serum urate target,” she said. “This is akin to finding the right regimen and titrating doses of medications for patients with diabetes or hypertension in a patient-centered manner.”
Patients in both groups developed mild increases in liver function tests, and a few in the dose escalation group developed more pronounced rises in gamma glutamyl transferase (GGT), as previously reported in the LASSO trial (Semin Arthritis Rheum. 2015 Oct;45[2]:174-83). Allopurinol has been linked to liver enzyme abnormalities, and the GGT finding is of unclear significance, but laboratory monitoring is important, Dr. Neogi said. If primary care providers who treat gout cannot routinely measure serum urate and other relevant laboratory measures, they should consider referring patients to a rheumatologist, she added.
Gradual dose escalation meant that patients did not reach the serum urate target until month 7, Dr. Neogi added. “Since the trial was 12 months long, the time over which serum urate was less than 6 mg/dL was not long enough to demonstrate the benefits on flares and tophi,” she said. The open-label extension phase of the trial should shed more insight on these important questions, she added.
For now, providers should know that “patients with gout are not well served if their serum urate levels remain elevated, as that means they are at ongoing risk for flares and tophi,” Dr. Neogi said. “This trial provides evidence and further support for the feasibility, efficacy, and relative safety of escalating allopurinol beyond creatinine-clearance dosing to achieve this important and critical goal for gout management.”
The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from the Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and the Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
Gradual dose escalation of allopurinol achieved target serum urate levels without causing excess adverse effects in patients with gout who tolerated but responded inadequately to creatinine clearance–based dosing, including in patients with chronic kidney disease, investigators reported in Annals of the Rheumatic Diseases.
The study is the first randomized, controlled trial to examine treat-to-target allopurinol dose escalation in gout. “We believe this approach can be undertaken in all patients who tolerate allopurinol,” lead investigator Lisa Stamp, MD, said in an interview. However, it is important to monitor kidney and liver function.”
To help settle these debates, Dr. Stamp and her associates recruited 183 patients with gout whose serum urate levels averaged 7.15 mg/dL (standard deviation, 1.6 mg/dL) despite at least 1 month of at least a creatinine clearance–based allopurinol dose (average, 269 mg/day). For the next 12 months, patients either continued this dose or increased it monthly until serum urate fell below 6 mg/dL (Ann Rheum Dis. 2017 March 17. doi: 10.1136/annrheumdis-2016-210872).
At month 12, 69% of dose-escalation patients and 32% of controls reached this target (P less than .001; odds ratio, 4.3; 95% confidence interval, 2.4-7.9). Serum urate levels dropped by a mean of 1.5 mg/dL with dose escalation and by 0.34 mg/dL in controls (P less than .001). Thus, dose escalation cut serum urate levels by an additional 1.2 mg/dL (95% CI, 0.67-1.5 mg/dL; P less than .001). The average final daily allopurinol dose was 413 mg (range, 0-900 mg) with dose escalation and 288 mg (0-600 mg) for controls.
Notably, renal function measures did not differ between arms. “There has been long-standing concern about whether it is safe to escalate allopurinol doses in persons with chronic kidney disease,” said Kenneth Saag, MD, of the University of Alabama at Birmingham, who was not involved in the trial. “This study contributes to the limited literature supporting the practice of treating to serum urate targets, even in patients with underlying kidney disease.”
Fully 52% of trial participants had chronic kidney disease, and 44% had tophi. “Thus, our population is representative of people with gout, represents real-life clinical practice, and the results are generalizable to other gout populations,” the investigators wrote.
The findings support the ACR recommendation to gradually titrate urate-lowering therapy while performing close laboratory monitoring, said Tuhina Neogi, MD, of Boston University, who was not involved in the study. This approach is “efficacious and relatively safe for patients who have already tolerated lower doses of allopurinol, but have not yet achieved their serum urate target,” she said. “This is akin to finding the right regimen and titrating doses of medications for patients with diabetes or hypertension in a patient-centered manner.”
Patients in both groups developed mild increases in liver function tests, and a few in the dose escalation group developed more pronounced rises in gamma glutamyl transferase (GGT), as previously reported in the LASSO trial (Semin Arthritis Rheum. 2015 Oct;45[2]:174-83). Allopurinol has been linked to liver enzyme abnormalities, and the GGT finding is of unclear significance, but laboratory monitoring is important, Dr. Neogi said. If primary care providers who treat gout cannot routinely measure serum urate and other relevant laboratory measures, they should consider referring patients to a rheumatologist, she added.
Gradual dose escalation meant that patients did not reach the serum urate target until month 7, Dr. Neogi added. “Since the trial was 12 months long, the time over which serum urate was less than 6 mg/dL was not long enough to demonstrate the benefits on flares and tophi,” she said. The open-label extension phase of the trial should shed more insight on these important questions, she added.
For now, providers should know that “patients with gout are not well served if their serum urate levels remain elevated, as that means they are at ongoing risk for flares and tophi,” Dr. Neogi said. “This trial provides evidence and further support for the feasibility, efficacy, and relative safety of escalating allopurinol beyond creatinine-clearance dosing to achieve this important and critical goal for gout management.”
The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from the Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and the Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
Gradual dose escalation of allopurinol achieved target serum urate levels without causing excess adverse effects in patients with gout who tolerated but responded inadequately to creatinine clearance–based dosing, including in patients with chronic kidney disease, investigators reported in Annals of the Rheumatic Diseases.
The study is the first randomized, controlled trial to examine treat-to-target allopurinol dose escalation in gout. “We believe this approach can be undertaken in all patients who tolerate allopurinol,” lead investigator Lisa Stamp, MD, said in an interview. However, it is important to monitor kidney and liver function.”
To help settle these debates, Dr. Stamp and her associates recruited 183 patients with gout whose serum urate levels averaged 7.15 mg/dL (standard deviation, 1.6 mg/dL) despite at least 1 month of at least a creatinine clearance–based allopurinol dose (average, 269 mg/day). For the next 12 months, patients either continued this dose or increased it monthly until serum urate fell below 6 mg/dL (Ann Rheum Dis. 2017 March 17. doi: 10.1136/annrheumdis-2016-210872).
At month 12, 69% of dose-escalation patients and 32% of controls reached this target (P less than .001; odds ratio, 4.3; 95% confidence interval, 2.4-7.9). Serum urate levels dropped by a mean of 1.5 mg/dL with dose escalation and by 0.34 mg/dL in controls (P less than .001). Thus, dose escalation cut serum urate levels by an additional 1.2 mg/dL (95% CI, 0.67-1.5 mg/dL; P less than .001). The average final daily allopurinol dose was 413 mg (range, 0-900 mg) with dose escalation and 288 mg (0-600 mg) for controls.
Notably, renal function measures did not differ between arms. “There has been long-standing concern about whether it is safe to escalate allopurinol doses in persons with chronic kidney disease,” said Kenneth Saag, MD, of the University of Alabama at Birmingham, who was not involved in the trial. “This study contributes to the limited literature supporting the practice of treating to serum urate targets, even in patients with underlying kidney disease.”
Fully 52% of trial participants had chronic kidney disease, and 44% had tophi. “Thus, our population is representative of people with gout, represents real-life clinical practice, and the results are generalizable to other gout populations,” the investigators wrote.
The findings support the ACR recommendation to gradually titrate urate-lowering therapy while performing close laboratory monitoring, said Tuhina Neogi, MD, of Boston University, who was not involved in the study. This approach is “efficacious and relatively safe for patients who have already tolerated lower doses of allopurinol, but have not yet achieved their serum urate target,” she said. “This is akin to finding the right regimen and titrating doses of medications for patients with diabetes or hypertension in a patient-centered manner.”
Patients in both groups developed mild increases in liver function tests, and a few in the dose escalation group developed more pronounced rises in gamma glutamyl transferase (GGT), as previously reported in the LASSO trial (Semin Arthritis Rheum. 2015 Oct;45[2]:174-83). Allopurinol has been linked to liver enzyme abnormalities, and the GGT finding is of unclear significance, but laboratory monitoring is important, Dr. Neogi said. If primary care providers who treat gout cannot routinely measure serum urate and other relevant laboratory measures, they should consider referring patients to a rheumatologist, she added.
Gradual dose escalation meant that patients did not reach the serum urate target until month 7, Dr. Neogi added. “Since the trial was 12 months long, the time over which serum urate was less than 6 mg/dL was not long enough to demonstrate the benefits on flares and tophi,” she said. The open-label extension phase of the trial should shed more insight on these important questions, she added.
For now, providers should know that “patients with gout are not well served if their serum urate levels remain elevated, as that means they are at ongoing risk for flares and tophi,” Dr. Neogi said. “This trial provides evidence and further support for the feasibility, efficacy, and relative safety of escalating allopurinol beyond creatinine-clearance dosing to achieve this important and critical goal for gout management.”
The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from the Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and the Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: At month 12, 69% of dose escalation patients and 32% of controls had serum urate levels below 6 mg/dL (P less than .001). Dose escalation did not increase the risk of serious adverse effects.
Data source: A 12-month, open-label, randomized, controlled, parallel-group, comparative trial of 186 patients with gout.
Disclosures: The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
CDC: Greater activity limitations accompany rising arthritis prevalence
The number of adults with arthritis in the United States continues to rise, with the number projected to climb as high as 78 million by the year 2040. Some of the keys to stemming this rising tide are exercise, along with greater knowledge of how to manage symptoms, according to a new report from the Centers for Disease Control and Prevention.
“Arthritis is at an all-time high: more than 54 million people report a diagnosis of it, and alarmingly, more people with arthritis are suffering from it,” said Anne Schuchat, MD, acting director of the CDC, during a conference call regarding the agency’s latest Vital Signs report (MMWR Morb Mortal Wkly Rep. 2017 Mar 7. doi: org/10.15585/mmwr.mm6609e1). “Among adults with arthritis, the percentage whose lives are particularly limited has increased by about 20% since 2002, from about 36% in 2002 to 43% in 2015. We’re seeing this increase independent of aging of the population.”
“Physical activity can be the antidote for many people [and] can actually decrease pain and improve function by almost 40%,” Dr. Schuchat explained. “Right now, one in three adults with arthritis report being inactive [because of] pain or fear of pain or not knowing what exercise is safe for their joints.”
This inactivity can lead to arthritis patients developing other serious chronic conditions, such as heart disease, diabetes and obesity – conditions that all require physical activity in order to properly manage them. Arthritis alone puts an extraordinary financial burden on the domestic health care industry, as direct medical costs associated with the condition total roughly $81 billion per year, according to the CDC. Additionally, about half of all adults with heart disease or diabetes, and about one-third of obese adults, also have arthritis.
In addition to engaging in regular physical activity, the Vital Signs report also recommends that arthritis patients attend disease management education programs, which are available regionally but often go underutilized, largely due to lack of awareness about them or trepidation regarding how effective the programs really are. To combat this, the CDC is calling on health care providers to help them educate patients about these classes and spread the word about the steps that can be taken to manage arthritis. In 2017, the CDC is funding arthritis programs in 12 states (California, Kansas, Kentucky, Michigan, Missouri, Montana, New York, Oregon, Pennsylvania, Rhode Island, South Carolina, and Utah) to disseminate arthritis-appropriate evidence-based physical activity and self-management education interventions.
“Men or women with arthritis can reduce their symptoms by 10%-20% by participating in disease management education programs to acquire skills to better manage their symptoms. Right now, these programs are only reaching about 1 in 10 people with arthritis, but the classes are available in many community settings,” Dr. Schuchat said. “We know that adults with arthritis are significantly more likely to attend a disease management education program when a health care provider recommends it to them.”
When seeing patients with arthritis, Dr. Schuchat advised health care providers to recommend routine physical activity, such as walking, biking, swimming, and physical activity programs offered by local parks and recreation centers, as well as weight loss, in order to ease joint pain. The American College of Rheumatology and other professional organizations provide guidelines for discussing treatment options with patients. Providing treatment or additional services for depression or anxiety, which occur in about one-third of adult arthritis patients, may help individuals to better manage their arthritis symptoms.
The agency’s report derives from its analysis of 2013-2015 data from the National Health Interview Survey, which comprised a nationally representative sample of about 36,000 in-person interviews. The survey classifies individuals with physician-diagnosed arthritis as those who answered “yes” to the question “Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?”
The number of adults with arthritis in the United States continues to rise, with the number projected to climb as high as 78 million by the year 2040. Some of the keys to stemming this rising tide are exercise, along with greater knowledge of how to manage symptoms, according to a new report from the Centers for Disease Control and Prevention.
“Arthritis is at an all-time high: more than 54 million people report a diagnosis of it, and alarmingly, more people with arthritis are suffering from it,” said Anne Schuchat, MD, acting director of the CDC, during a conference call regarding the agency’s latest Vital Signs report (MMWR Morb Mortal Wkly Rep. 2017 Mar 7. doi: org/10.15585/mmwr.mm6609e1). “Among adults with arthritis, the percentage whose lives are particularly limited has increased by about 20% since 2002, from about 36% in 2002 to 43% in 2015. We’re seeing this increase independent of aging of the population.”
“Physical activity can be the antidote for many people [and] can actually decrease pain and improve function by almost 40%,” Dr. Schuchat explained. “Right now, one in three adults with arthritis report being inactive [because of] pain or fear of pain or not knowing what exercise is safe for their joints.”
This inactivity can lead to arthritis patients developing other serious chronic conditions, such as heart disease, diabetes and obesity – conditions that all require physical activity in order to properly manage them. Arthritis alone puts an extraordinary financial burden on the domestic health care industry, as direct medical costs associated with the condition total roughly $81 billion per year, according to the CDC. Additionally, about half of all adults with heart disease or diabetes, and about one-third of obese adults, also have arthritis.
In addition to engaging in regular physical activity, the Vital Signs report also recommends that arthritis patients attend disease management education programs, which are available regionally but often go underutilized, largely due to lack of awareness about them or trepidation regarding how effective the programs really are. To combat this, the CDC is calling on health care providers to help them educate patients about these classes and spread the word about the steps that can be taken to manage arthritis. In 2017, the CDC is funding arthritis programs in 12 states (California, Kansas, Kentucky, Michigan, Missouri, Montana, New York, Oregon, Pennsylvania, Rhode Island, South Carolina, and Utah) to disseminate arthritis-appropriate evidence-based physical activity and self-management education interventions.
“Men or women with arthritis can reduce their symptoms by 10%-20% by participating in disease management education programs to acquire skills to better manage their symptoms. Right now, these programs are only reaching about 1 in 10 people with arthritis, but the classes are available in many community settings,” Dr. Schuchat said. “We know that adults with arthritis are significantly more likely to attend a disease management education program when a health care provider recommends it to them.”
When seeing patients with arthritis, Dr. Schuchat advised health care providers to recommend routine physical activity, such as walking, biking, swimming, and physical activity programs offered by local parks and recreation centers, as well as weight loss, in order to ease joint pain. The American College of Rheumatology and other professional organizations provide guidelines for discussing treatment options with patients. Providing treatment or additional services for depression or anxiety, which occur in about one-third of adult arthritis patients, may help individuals to better manage their arthritis symptoms.
The agency’s report derives from its analysis of 2013-2015 data from the National Health Interview Survey, which comprised a nationally representative sample of about 36,000 in-person interviews. The survey classifies individuals with physician-diagnosed arthritis as those who answered “yes” to the question “Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?”
The number of adults with arthritis in the United States continues to rise, with the number projected to climb as high as 78 million by the year 2040. Some of the keys to stemming this rising tide are exercise, along with greater knowledge of how to manage symptoms, according to a new report from the Centers for Disease Control and Prevention.
“Arthritis is at an all-time high: more than 54 million people report a diagnosis of it, and alarmingly, more people with arthritis are suffering from it,” said Anne Schuchat, MD, acting director of the CDC, during a conference call regarding the agency’s latest Vital Signs report (MMWR Morb Mortal Wkly Rep. 2017 Mar 7. doi: org/10.15585/mmwr.mm6609e1). “Among adults with arthritis, the percentage whose lives are particularly limited has increased by about 20% since 2002, from about 36% in 2002 to 43% in 2015. We’re seeing this increase independent of aging of the population.”
“Physical activity can be the antidote for many people [and] can actually decrease pain and improve function by almost 40%,” Dr. Schuchat explained. “Right now, one in three adults with arthritis report being inactive [because of] pain or fear of pain or not knowing what exercise is safe for their joints.”
This inactivity can lead to arthritis patients developing other serious chronic conditions, such as heart disease, diabetes and obesity – conditions that all require physical activity in order to properly manage them. Arthritis alone puts an extraordinary financial burden on the domestic health care industry, as direct medical costs associated with the condition total roughly $81 billion per year, according to the CDC. Additionally, about half of all adults with heart disease or diabetes, and about one-third of obese adults, also have arthritis.
In addition to engaging in regular physical activity, the Vital Signs report also recommends that arthritis patients attend disease management education programs, which are available regionally but often go underutilized, largely due to lack of awareness about them or trepidation regarding how effective the programs really are. To combat this, the CDC is calling on health care providers to help them educate patients about these classes and spread the word about the steps that can be taken to manage arthritis. In 2017, the CDC is funding arthritis programs in 12 states (California, Kansas, Kentucky, Michigan, Missouri, Montana, New York, Oregon, Pennsylvania, Rhode Island, South Carolina, and Utah) to disseminate arthritis-appropriate evidence-based physical activity and self-management education interventions.
“Men or women with arthritis can reduce their symptoms by 10%-20% by participating in disease management education programs to acquire skills to better manage their symptoms. Right now, these programs are only reaching about 1 in 10 people with arthritis, but the classes are available in many community settings,” Dr. Schuchat said. “We know that adults with arthritis are significantly more likely to attend a disease management education program when a health care provider recommends it to them.”
When seeing patients with arthritis, Dr. Schuchat advised health care providers to recommend routine physical activity, such as walking, biking, swimming, and physical activity programs offered by local parks and recreation centers, as well as weight loss, in order to ease joint pain. The American College of Rheumatology and other professional organizations provide guidelines for discussing treatment options with patients. Providing treatment or additional services for depression or anxiety, which occur in about one-third of adult arthritis patients, may help individuals to better manage their arthritis symptoms.
The agency’s report derives from its analysis of 2013-2015 data from the National Health Interview Survey, which comprised a nationally representative sample of about 36,000 in-person interviews. The survey classifies individuals with physician-diagnosed arthritis as those who answered “yes” to the question “Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?”
FROM MMWR
Key clinical point:
Major finding: About 24 million American adults report being significantly limited due to their arthritis.
Data source: 2013-2015 data from the National Health Interview Survey.
Disclosures: No disclosures were reported.
VIDEO: Urate lowering therapy improved kidney function
WASHINGTON – Urate lowering therapy improved kidney function in patients with chronic kidney disease (CKD), according to a large retrospective study presented at the annual meeting of the American College of Rheumatology. Moreover, patients with CKD stage 3 derived the most benefit from urate lowering therapy, and those with CKD stage 2 also benefited to a lesser degree. Patients with CKD stage 4 had no benefit from urate lowering therapy.
“Two years ago we showed that urate lowering therapy did not worsen kidney function in patients with chronic kidney disease. This study shows that their kidney function improved [with urate lowering therapy],” said Gerald D. Levy, MD, MBA, a rheumatologist at Kaiser Permanente of Southern California, Downey, Calif.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of above 7 mg/dL and CKD Stages 2, 3, and 4 at the index date, defined as the first time this test result was reported. Patients were drawn from the Kaiser Permanente database and were treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on urate lowering therapy and 10,061 were not on urate lowering therapy. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on urate lowering therapy. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve sUA goal, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate lowering therapy,” he stated. “Stage 4 CKD is too late.”
Dr. Levy discussed the findings in a video interview during the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Urate lowering therapy improved kidney function in patients with chronic kidney disease (CKD), according to a large retrospective study presented at the annual meeting of the American College of Rheumatology. Moreover, patients with CKD stage 3 derived the most benefit from urate lowering therapy, and those with CKD stage 2 also benefited to a lesser degree. Patients with CKD stage 4 had no benefit from urate lowering therapy.
“Two years ago we showed that urate lowering therapy did not worsen kidney function in patients with chronic kidney disease. This study shows that their kidney function improved [with urate lowering therapy],” said Gerald D. Levy, MD, MBA, a rheumatologist at Kaiser Permanente of Southern California, Downey, Calif.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of above 7 mg/dL and CKD Stages 2, 3, and 4 at the index date, defined as the first time this test result was reported. Patients were drawn from the Kaiser Permanente database and were treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on urate lowering therapy and 10,061 were not on urate lowering therapy. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on urate lowering therapy. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve sUA goal, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate lowering therapy,” he stated. “Stage 4 CKD is too late.”
Dr. Levy discussed the findings in a video interview during the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Urate lowering therapy improved kidney function in patients with chronic kidney disease (CKD), according to a large retrospective study presented at the annual meeting of the American College of Rheumatology. Moreover, patients with CKD stage 3 derived the most benefit from urate lowering therapy, and those with CKD stage 2 also benefited to a lesser degree. Patients with CKD stage 4 had no benefit from urate lowering therapy.
“Two years ago we showed that urate lowering therapy did not worsen kidney function in patients with chronic kidney disease. This study shows that their kidney function improved [with urate lowering therapy],” said Gerald D. Levy, MD, MBA, a rheumatologist at Kaiser Permanente of Southern California, Downey, Calif.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of above 7 mg/dL and CKD Stages 2, 3, and 4 at the index date, defined as the first time this test result was reported. Patients were drawn from the Kaiser Permanente database and were treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on urate lowering therapy and 10,061 were not on urate lowering therapy. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on urate lowering therapy. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve sUA goal, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate lowering therapy,” he stated. “Stage 4 CKD is too late.”
Dr. Levy discussed the findings in a video interview during the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ACR ANNUAL MEETING
