Denise Napoli

WASHINGTON – Do you Twitter?

That was the question posed by Dr. Christopher Collins at the annual meeting of the American College of Rheumatology, and it wasn’t an idle query. According to Dr. Collins, the social media site and other mobile, Web-based media tools are poised to become the next big thing in rheumatology education.

"The next generation of rheumatology fellows has already embraced mobile technology as an important aspect of not only everyday life, but as a tool to augment their education," said Dr. Collins, director of the fellowship program for the division of rheumatology at Washington (D.C.) Hospital.

Denise Napoli/IMNG Medical Media

"Social media outlets such as Twitter provide a means for interactions which are not limited by geography, and provide a potential means to enhance the education experience."

At the meeting, Dr. Collins presented proof of concept: His Twitter feed, @RheumPearls, offers a (roughly) daily, 140-character rheumatology "pearl of wisdom" on topics including arthritis, lupus, and gout.

The development of his feed was supported by a grant from the ACR’s Rheumatology Research Foundation, awarded to Dr. Collins in 2010. The Clinician Scholar Educator award aims to further the development of new teaching strategies in rheumatology, according to the ACR’s website.

Founded in March 2011, Dr. Collins’s Twitter feed has nearly 1,000 followers from 57 different countries, with 434 tweets posted at the time of his presentation.

In an analysis of his first 100 followers, Dr. Collins calculated that 25% were physicians (61% of whom were rheumatologists), 23% were patients with self-identified rheumatic conditions (especially lupus and rheumatoid arthritis), 18% were professional medical organizations, and 11% were medical trainees, including medical students, residents, and fellows.

The remainder were unidentified or affiliated with the pharmaceutical industry.

A website Dr. Collins created to complement the Twitter feed has also garnered attention, with 8,125 page views and 6,500 unique visitors from 102 different countries at the time of his presentation.

According to Dr. Collins, his Twitter feed represents just one of the myriad ways in which the social media site, and sites like it, could be used to educate and inform students as well as practitioners of rheumatology.

For example, he pointed to the ways in which Twitter is already used at the ACR’s annual meeting.

"With the use of hashtags, tweets can be ‘tagged’ for searching relevant topics," said Dr. Collins in an e-mail interview.

"During the ACR, searching ‘#ACR2012’ revealed all the relevant tweets being posted about the conference for participants to follow."

In the future, "after a presentation on a particular topic has ended, discussion points can be posted to Twitter for comment by the participants," he said.

In addition, "the participants can continue to be part of the discussion even after the original presentation has ended, as long as they have access to the Internet (as most do with their mobile devices)," Dr. Collins noted.

The technology can also foster more individualized education, even as it reaches out readily to the vast network of Twitter users.

"A mentor who is willing to engage their learners through social media like Twitter can increase their availability to students and augment interactions through direct conversations, and provide links to literature, etc.," he said.

"In addition to purely informative educational Twitter feeds like mine, I see Twitter as having the potential to engage a global population interested in rheumatology and rheumatology education through live interactive discussions."

Dr. Collins disclosed being on a speakers bureau for GlaxoSmithKline and Abbott Laboratories. He stated that he had nothing to disclose relevant to the development and implementation of RheumPearls.

WASHINGTON – Do you Twitter?

That was the question posed by Dr. Christopher Collins at the annual meeting of the American College of Rheumatology, and it wasn’t an idle query. According to Dr. Collins, the social media site and other mobile, Web-based media tools are poised to become the next big thing in rheumatology education.

"The next generation of rheumatology fellows has already embraced mobile technology as an important aspect of not only everyday life, but as a tool to augment their education," said Dr. Collins, director of the fellowship program for the division of rheumatology at Washington (D.C.) Hospital.

Denise Napoli/IMNG Medical Media

"Social media outlets such as Twitter provide a means for interactions which are not limited by geography, and provide a potential means to enhance the education experience."

At the meeting, Dr. Collins presented proof of concept: His Twitter feed, @RheumPearls, offers a (roughly) daily, 140-character rheumatology "pearl of wisdom" on topics including arthritis, lupus, and gout.

The development of his feed was supported by a grant from the ACR’s Rheumatology Research Foundation, awarded to Dr. Collins in 2010. The Clinician Scholar Educator award aims to further the development of new teaching strategies in rheumatology, according to the ACR’s website.

Founded in March 2011, Dr. Collins’s Twitter feed has nearly 1,000 followers from 57 different countries, with 434 tweets posted at the time of his presentation.

In an analysis of his first 100 followers, Dr. Collins calculated that 25% were physicians (61% of whom were rheumatologists), 23% were patients with self-identified rheumatic conditions (especially lupus and rheumatoid arthritis), 18% were professional medical organizations, and 11% were medical trainees, including medical students, residents, and fellows.

The remainder were unidentified or affiliated with the pharmaceutical industry.

A website Dr. Collins created to complement the Twitter feed has also garnered attention, with 8,125 page views and 6,500 unique visitors from 102 different countries at the time of his presentation.

According to Dr. Collins, his Twitter feed represents just one of the myriad ways in which the social media site, and sites like it, could be used to educate and inform students as well as practitioners of rheumatology.

For example, he pointed to the ways in which Twitter is already used at the ACR’s annual meeting.

"With the use of hashtags, tweets can be ‘tagged’ for searching relevant topics," said Dr. Collins in an e-mail interview.

"During the ACR, searching ‘#ACR2012’ revealed all the relevant tweets being posted about the conference for participants to follow."

In the future, "after a presentation on a particular topic has ended, discussion points can be posted to Twitter for comment by the participants," he said.

In addition, "the participants can continue to be part of the discussion even after the original presentation has ended, as long as they have access to the Internet (as most do with their mobile devices)," Dr. Collins noted.

The technology can also foster more individualized education, even as it reaches out readily to the vast network of Twitter users.

"A mentor who is willing to engage their learners through social media like Twitter can increase their availability to students and augment interactions through direct conversations, and provide links to literature, etc.," he said.

"In addition to purely informative educational Twitter feeds like mine, I see Twitter as having the potential to engage a global population interested in rheumatology and rheumatology education through live interactive discussions."

Dr. Collins disclosed being on a speakers bureau for GlaxoSmithKline and Abbott Laboratories. He stated that he had nothing to disclose relevant to the development and implementation of RheumPearls.

WASHINGTON – Do you Twitter?

That was the question posed by Dr. Christopher Collins at the annual meeting of the American College of Rheumatology, and it wasn’t an idle query. According to Dr. Collins, the social media site and other mobile, Web-based media tools are poised to become the next big thing in rheumatology education.

"The next generation of rheumatology fellows has already embraced mobile technology as an important aspect of not only everyday life, but as a tool to augment their education," said Dr. Collins, director of the fellowship program for the division of rheumatology at Washington (D.C.) Hospital.

Denise Napoli/IMNG Medical Media

"Social media outlets such as Twitter provide a means for interactions which are not limited by geography, and provide a potential means to enhance the education experience."

At the meeting, Dr. Collins presented proof of concept: His Twitter feed, @RheumPearls, offers a (roughly) daily, 140-character rheumatology "pearl of wisdom" on topics including arthritis, lupus, and gout.

The development of his feed was supported by a grant from the ACR’s Rheumatology Research Foundation, awarded to Dr. Collins in 2010. The Clinician Scholar Educator award aims to further the development of new teaching strategies in rheumatology, according to the ACR’s website.

Founded in March 2011, Dr. Collins’s Twitter feed has nearly 1,000 followers from 57 different countries, with 434 tweets posted at the time of his presentation.

In an analysis of his first 100 followers, Dr. Collins calculated that 25% were physicians (61% of whom were rheumatologists), 23% were patients with self-identified rheumatic conditions (especially lupus and rheumatoid arthritis), 18% were professional medical organizations, and 11% were medical trainees, including medical students, residents, and fellows.

The remainder were unidentified or affiliated with the pharmaceutical industry.

A website Dr. Collins created to complement the Twitter feed has also garnered attention, with 8,125 page views and 6,500 unique visitors from 102 different countries at the time of his presentation.

According to Dr. Collins, his Twitter feed represents just one of the myriad ways in which the social media site, and sites like it, could be used to educate and inform students as well as practitioners of rheumatology.

For example, he pointed to the ways in which Twitter is already used at the ACR’s annual meeting.

"With the use of hashtags, tweets can be ‘tagged’ for searching relevant topics," said Dr. Collins in an e-mail interview.

"During the ACR, searching ‘#ACR2012’ revealed all the relevant tweets being posted about the conference for participants to follow."

In the future, "after a presentation on a particular topic has ended, discussion points can be posted to Twitter for comment by the participants," he said.

In addition, "the participants can continue to be part of the discussion even after the original presentation has ended, as long as they have access to the Internet (as most do with their mobile devices)," Dr. Collins noted.

The technology can also foster more individualized education, even as it reaches out readily to the vast network of Twitter users.

"A mentor who is willing to engage their learners through social media like Twitter can increase their availability to students and augment interactions through direct conversations, and provide links to literature, etc.," he said.

"In addition to purely informative educational Twitter feeds like mine, I see Twitter as having the potential to engage a global population interested in rheumatology and rheumatology education through live interactive discussions."

Dr. Collins disclosed being on a speakers bureau for GlaxoSmithKline and Abbott Laboratories. He stated that he had nothing to disclose relevant to the development and implementation of RheumPearls.

WASHINGTON – Autoantibody seronegativity may be the best predictor of which patients will achieve remission in rheumatoid arthritis, but the question of whether and when to withdraw treatment still looms.

"Drug-free remission is possible. Sustained remission is less common," Dr. Stanley Cohen said at the annual meeting of the American College of Rheumatology. "But certainly seronegativity seems to be a strong predictor of the likelihood of sustained remission."

Denise Napoli/IMNG Medical Media

First, Dr. Cohen of Metroplex Clinical Research Center, Dallas, cited several "prebiologic era" studies, including one 1996 randomized controlled trial of 285 patients who stopped nonbiological disease-modifying antirheumatic drug (DMARD) therapy after achieving the "quite stringent" 1981 ACR/ARA remission definitions for 1 year.

In that study, after the year of remission, patients were randomized to either placebo or to continue their treatment regimen: by 52 weeks, 38% of the placebo group had flared, compared with 22% of the continued therapy group (P = .002) (Lancet 1996;347:347-52).

The authors then looked at the predictors of maintaining remission.

"They determined that having rheumatoid factor activity [there were no CCP (cyclic citrullinated peptide) antibodies at that time] was a poor prognostic factor for maintaining remission," said Dr. Cohen.

"More aggressive treatment prior to remission also boded poorly for maintaining that remission," he noted.

A similar finding was seen with the Leiden Early Arthritis Clinic trial of 454 patients and the British Early Rheumatoid Arthritis Study (ERAS) of 895 patients, both reviewed in 2009.

Sustained drug-free remission was seen in 15% of the former cohort and in 9% in the latter. The absences of CCP autoantibodies and rheumatoid factor were the sole two independent predictors of remission in multivariate analysis (Arthritis Rheum. 2009;60:2262-71).

Having early disease also plays a role in the ability to withdraw treatment, Dr. Cohen said. He pointed to the COMET trial (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis), which looked at etanercept plus methotrexate versus methotrexate alone in moderate-to-severe rheumatoid arthritis for a duration of 3-24 months.

"What I’m interested in is year 2," Dr. Cohen said, when 111 patients who were on methotrexate plus etanercept in year 1 stopped methotrexate (Arthritis Rheum. 2010;62:674-82).

"Compared to the group that continued etanercept plus methotrexate, the majority continued to be in DAS28 remission without methotrexate" at 2 years, he said. "So, in patients with very early disease, it looks like we can withdraw or simplify the therapy in a significant number of those patients."

Treatment withdrawal, however, also can be achieved in patients with more longstanding disease.

Dr. Cohen cited a 2003 long-term extension of a clinical registration trial in which 79 patients with very long and very severe disease (mean duration of disease, 14 years) received etanercept and methotrexate for a median of 44 months (Arthritis Rheum. 2003;48:1493-9).

Among the 36 patients assessed at 3 years, 30 (83%) were able to decrease their dosages of corticosteroids and 20 (56%) could stop corticosteroids altogether.

"This certainly follows what we see in the clinic, in that we can frequently lower our doses of corticosteroids or withdraw them," Dr. Cohen said.

"What about methotrexate?" he asked. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).

"We try to wean our therapy in the majority of these patients," said Dr. Cohen. "Some are successful, some are not."

Dr. Cohen stated that he had no disclosures related to this presentation; he previously disclosed relationships with Abbott Laboratories, Amgen, Astellas, Bristol-Myers Squibb, Janssen, Pfizer, and Roche.

WASHINGTON – Autoantibody seronegativity may be the best predictor of which patients will achieve remission in rheumatoid arthritis, but the question of whether and when to withdraw treatment still looms.

"Drug-free remission is possible. Sustained remission is less common," Dr. Stanley Cohen said at the annual meeting of the American College of Rheumatology. "But certainly seronegativity seems to be a strong predictor of the likelihood of sustained remission."

Denise Napoli/IMNG Medical Media

First, Dr. Cohen of Metroplex Clinical Research Center, Dallas, cited several "prebiologic era" studies, including one 1996 randomized controlled trial of 285 patients who stopped nonbiological disease-modifying antirheumatic drug (DMARD) therapy after achieving the "quite stringent" 1981 ACR/ARA remission definitions for 1 year.

In that study, after the year of remission, patients were randomized to either placebo or to continue their treatment regimen: by 52 weeks, 38% of the placebo group had flared, compared with 22% of the continued therapy group (P = .002) (Lancet 1996;347:347-52).

The authors then looked at the predictors of maintaining remission.

"They determined that having rheumatoid factor activity [there were no CCP (cyclic citrullinated peptide) antibodies at that time] was a poor prognostic factor for maintaining remission," said Dr. Cohen.

"More aggressive treatment prior to remission also boded poorly for maintaining that remission," he noted.

A similar finding was seen with the Leiden Early Arthritis Clinic trial of 454 patients and the British Early Rheumatoid Arthritis Study (ERAS) of 895 patients, both reviewed in 2009.

Sustained drug-free remission was seen in 15% of the former cohort and in 9% in the latter. The absences of CCP autoantibodies and rheumatoid factor were the sole two independent predictors of remission in multivariate analysis (Arthritis Rheum. 2009;60:2262-71).

Having early disease also plays a role in the ability to withdraw treatment, Dr. Cohen said. He pointed to the COMET trial (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis), which looked at etanercept plus methotrexate versus methotrexate alone in moderate-to-severe rheumatoid arthritis for a duration of 3-24 months.

"What I’m interested in is year 2," Dr. Cohen said, when 111 patients who were on methotrexate plus etanercept in year 1 stopped methotrexate (Arthritis Rheum. 2010;62:674-82).

"Compared to the group that continued etanercept plus methotrexate, the majority continued to be in DAS28 remission without methotrexate" at 2 years, he said. "So, in patients with very early disease, it looks like we can withdraw or simplify the therapy in a significant number of those patients."

Treatment withdrawal, however, also can be achieved in patients with more longstanding disease.

Dr. Cohen cited a 2003 long-term extension of a clinical registration trial in which 79 patients with very long and very severe disease (mean duration of disease, 14 years) received etanercept and methotrexate for a median of 44 months (Arthritis Rheum. 2003;48:1493-9).

Among the 36 patients assessed at 3 years, 30 (83%) were able to decrease their dosages of corticosteroids and 20 (56%) could stop corticosteroids altogether.

"This certainly follows what we see in the clinic, in that we can frequently lower our doses of corticosteroids or withdraw them," Dr. Cohen said.

"What about methotrexate?" he asked. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).

"We try to wean our therapy in the majority of these patients," said Dr. Cohen. "Some are successful, some are not."

Dr. Cohen stated that he had no disclosures related to this presentation; he previously disclosed relationships with Abbott Laboratories, Amgen, Astellas, Bristol-Myers Squibb, Janssen, Pfizer, and Roche.

WASHINGTON – Autoantibody seronegativity may be the best predictor of which patients will achieve remission in rheumatoid arthritis, but the question of whether and when to withdraw treatment still looms.

"Drug-free remission is possible. Sustained remission is less common," Dr. Stanley Cohen said at the annual meeting of the American College of Rheumatology. "But certainly seronegativity seems to be a strong predictor of the likelihood of sustained remission."

Denise Napoli/IMNG Medical Media

First, Dr. Cohen of Metroplex Clinical Research Center, Dallas, cited several "prebiologic era" studies, including one 1996 randomized controlled trial of 285 patients who stopped nonbiological disease-modifying antirheumatic drug (DMARD) therapy after achieving the "quite stringent" 1981 ACR/ARA remission definitions for 1 year.

In that study, after the year of remission, patients were randomized to either placebo or to continue their treatment regimen: by 52 weeks, 38% of the placebo group had flared, compared with 22% of the continued therapy group (P = .002) (Lancet 1996;347:347-52).

The authors then looked at the predictors of maintaining remission.

"They determined that having rheumatoid factor activity [there were no CCP (cyclic citrullinated peptide) antibodies at that time] was a poor prognostic factor for maintaining remission," said Dr. Cohen.

"More aggressive treatment prior to remission also boded poorly for maintaining that remission," he noted.

A similar finding was seen with the Leiden Early Arthritis Clinic trial of 454 patients and the British Early Rheumatoid Arthritis Study (ERAS) of 895 patients, both reviewed in 2009.

Sustained drug-free remission was seen in 15% of the former cohort and in 9% in the latter. The absences of CCP autoantibodies and rheumatoid factor were the sole two independent predictors of remission in multivariate analysis (Arthritis Rheum. 2009;60:2262-71).

Having early disease also plays a role in the ability to withdraw treatment, Dr. Cohen said. He pointed to the COMET trial (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis), which looked at etanercept plus methotrexate versus methotrexate alone in moderate-to-severe rheumatoid arthritis for a duration of 3-24 months.

"What I’m interested in is year 2," Dr. Cohen said, when 111 patients who were on methotrexate plus etanercept in year 1 stopped methotrexate (Arthritis Rheum. 2010;62:674-82).

"Compared to the group that continued etanercept plus methotrexate, the majority continued to be in DAS28 remission without methotrexate" at 2 years, he said. "So, in patients with very early disease, it looks like we can withdraw or simplify the therapy in a significant number of those patients."

Treatment withdrawal, however, also can be achieved in patients with more longstanding disease.

Dr. Cohen cited a 2003 long-term extension of a clinical registration trial in which 79 patients with very long and very severe disease (mean duration of disease, 14 years) received etanercept and methotrexate for a median of 44 months (Arthritis Rheum. 2003;48:1493-9).

Among the 36 patients assessed at 3 years, 30 (83%) were able to decrease their dosages of corticosteroids and 20 (56%) could stop corticosteroids altogether.

"This certainly follows what we see in the clinic, in that we can frequently lower our doses of corticosteroids or withdraw them," Dr. Cohen said.

"What about methotrexate?" he asked. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).

"We try to wean our therapy in the majority of these patients," said Dr. Cohen. "Some are successful, some are not."

Dr. Cohen stated that he had no disclosures related to this presentation; he previously disclosed relationships with Abbott Laboratories, Amgen, Astellas, Bristol-Myers Squibb, Janssen, Pfizer, and Roche.

WASHINGTON – "Blanket" monitoring guidelines for liver toxicity in patients taking methotrexate may do more harm than good.

That’s according to Dr. Gabriela Schmajuk, who found that up to a third of patients taking the drug for rheumatoid arthritis may have the drug discontinued unnecessarily in the presence of mildly elevated liver function tests (LFTs).

"We need more research to say what the best strategies are [when it comes to] LFT monitoring, and what our response to abnormal LFTs should be," she said at the annual meeting of the American College of Rheumatology.

In a poster presented at the meeting, Dr. Schmajuk of the University of California, San Francisco, and her colleagues looked at 899 new methotrexate users (97% male, mean age 71 years) aged 65 years and older treated at the Veterans Health Administration (VHA) during 2007-2008.

The study was conducted in response to the recent measure issued by the National Quality Forum, which assesses whether rheumatoid arthritis patients prescribed methotrexate received an LFT within 120 days of their prescription claim. The measure is for public quality reporting purposes.

First, Dr. Schmajuk looked at how many patients met the National Quality Forum’s measure.

Patients all had at least a 28-day supply of methotrexate with follow-up at the VHA for 3 months after the drug was dispensed.

Patients were excluded from the study if they had any diagnosis of inflammatory bowel disease or if they sought medical care outside the VHA, and the researchers correlated the first abnormal LFT with the rate of methotrexate discontinuation.

Overall, they found that 148 patients (16.5%) did not have any LFT testing after methotrexate was initiated.

Among the patients who did have their LFTs monitored, 136 (15.1%) had any abnormality of AST or ALT, and only 49 patients (5%) had an elevation of at least 1.5 times the upper limit of normal; among these, methotrexate was discontinued in 27 patients.

However, the researchers also found that methotrexate was discontinued in 28 (32%) of 87 patients with LFT elevations less than 1.5 times the upper limit of normal.

In an e-mail interview, Dr. Schmajuk conceded that a full chart review on these patients has not yet been completed, and that "it is entirely possible that patients were discontinuing [methotrexate] for reasons not related to the LFTs."

However, "We need more research to help decide what a safe cutoff of discontinuation should be – it is possible that it is higher than previously thought."

She added: "In the future, we should be able to tailor monitoring frequency to individual patients."

A second poster, also presented at the meeting, offered a step forward toward just that.

In that study, Dr. Monica Ramirez of Brigham and Women’s Hospital, Boston, attempted to identify clinical predictors of liver enzyme elevation in methotrexate-treated rheumatoid arthritis patients.

Dr. Ramirez and her colleagues conducted detailed chart evaluations of 500 rheumatoid arthritis patients treated at a single center since 1992 who were identified as ever having received treatment with methotrexate and who had LFTs greater than two times the upper limit of normal.

Patients were excluded if they had ever been diagnosed with hepatitis or any other liver disease, or if they had any concurrent hospital or clinic visits for cardiac disease, sepsis, acute kidney disease, metastatic cancer, trauma, or surgery.

A total of 90 (18%) cases were confirmed as having LFT elevations attributed to methotrexate usage.

The authors then assessed the relationship between several known risk factors for liver toxicity to see whether any of them predicted methotrexate dose reduction or discontinuation: age, sex, obesity, hyperlipidemia, methotrexate dose (2.5-7.5 mg, 10-17.5 mg, or 20-25 mg), alcohol use, statin use, and NSAID use.

In univariate analysis, only obesity was significantly associated with a likelihood of methotrexate discontinuation or dose reduction (odds ratio, 2.89; 95% confidence interval, 1.20-7.00; P = .02). Similarly, in multivariate analysis, obesity was the lone predictor (OR, 2.60; 95% CI, 1.01-6.66; P = .05).

"This suggests a potentially heightened risk of hepatotoxicity among obese patients," the authors concluded.

Dr. Schmajuk and her fellow researchers reported no disclosures and no outside funding for their study. The authors of the second study, led by Dr. Ramirez, reported funding from the National Institutes of Health, and one of the investigators reported financial support from Amgen, Abbott, and other companies.

WASHINGTON – "Blanket" monitoring guidelines for liver toxicity in patients taking methotrexate may do more harm than good.

That’s according to Dr. Gabriela Schmajuk, who found that up to a third of patients taking the drug for rheumatoid arthritis may have the drug discontinued unnecessarily in the presence of mildly elevated liver function tests (LFTs).

"We need more research to say what the best strategies are [when it comes to] LFT monitoring, and what our response to abnormal LFTs should be," she said at the annual meeting of the American College of Rheumatology.

In a poster presented at the meeting, Dr. Schmajuk of the University of California, San Francisco, and her colleagues looked at 899 new methotrexate users (97% male, mean age 71 years) aged 65 years and older treated at the Veterans Health Administration (VHA) during 2007-2008.

The study was conducted in response to the recent measure issued by the National Quality Forum, which assesses whether rheumatoid arthritis patients prescribed methotrexate received an LFT within 120 days of their prescription claim. The measure is for public quality reporting purposes.

First, Dr. Schmajuk looked at how many patients met the National Quality Forum’s measure.

Patients all had at least a 28-day supply of methotrexate with follow-up at the VHA for 3 months after the drug was dispensed.

Patients were excluded from the study if they had any diagnosis of inflammatory bowel disease or if they sought medical care outside the VHA, and the researchers correlated the first abnormal LFT with the rate of methotrexate discontinuation.

Overall, they found that 148 patients (16.5%) did not have any LFT testing after methotrexate was initiated.

Among the patients who did have their LFTs monitored, 136 (15.1%) had any abnormality of AST or ALT, and only 49 patients (5%) had an elevation of at least 1.5 times the upper limit of normal; among these, methotrexate was discontinued in 27 patients.

However, the researchers also found that methotrexate was discontinued in 28 (32%) of 87 patients with LFT elevations less than 1.5 times the upper limit of normal.

In an e-mail interview, Dr. Schmajuk conceded that a full chart review on these patients has not yet been completed, and that "it is entirely possible that patients were discontinuing [methotrexate] for reasons not related to the LFTs."

However, "We need more research to help decide what a safe cutoff of discontinuation should be – it is possible that it is higher than previously thought."

She added: "In the future, we should be able to tailor monitoring frequency to individual patients."

A second poster, also presented at the meeting, offered a step forward toward just that.

In that study, Dr. Monica Ramirez of Brigham and Women’s Hospital, Boston, attempted to identify clinical predictors of liver enzyme elevation in methotrexate-treated rheumatoid arthritis patients.

Dr. Ramirez and her colleagues conducted detailed chart evaluations of 500 rheumatoid arthritis patients treated at a single center since 1992 who were identified as ever having received treatment with methotrexate and who had LFTs greater than two times the upper limit of normal.

Patients were excluded if they had ever been diagnosed with hepatitis or any other liver disease, or if they had any concurrent hospital or clinic visits for cardiac disease, sepsis, acute kidney disease, metastatic cancer, trauma, or surgery.

A total of 90 (18%) cases were confirmed as having LFT elevations attributed to methotrexate usage.

The authors then assessed the relationship between several known risk factors for liver toxicity to see whether any of them predicted methotrexate dose reduction or discontinuation: age, sex, obesity, hyperlipidemia, methotrexate dose (2.5-7.5 mg, 10-17.5 mg, or 20-25 mg), alcohol use, statin use, and NSAID use.

In univariate analysis, only obesity was significantly associated with a likelihood of methotrexate discontinuation or dose reduction (odds ratio, 2.89; 95% confidence interval, 1.20-7.00; P = .02). Similarly, in multivariate analysis, obesity was the lone predictor (OR, 2.60; 95% CI, 1.01-6.66; P = .05).

"This suggests a potentially heightened risk of hepatotoxicity among obese patients," the authors concluded.

Dr. Schmajuk and her fellow researchers reported no disclosures and no outside funding for their study. The authors of the second study, led by Dr. Ramirez, reported funding from the National Institutes of Health, and one of the investigators reported financial support from Amgen, Abbott, and other companies.

WASHINGTON – "Blanket" monitoring guidelines for liver toxicity in patients taking methotrexate may do more harm than good.

That’s according to Dr. Gabriela Schmajuk, who found that up to a third of patients taking the drug for rheumatoid arthritis may have the drug discontinued unnecessarily in the presence of mildly elevated liver function tests (LFTs).

"We need more research to say what the best strategies are [when it comes to] LFT monitoring, and what our response to abnormal LFTs should be," she said at the annual meeting of the American College of Rheumatology.

In a poster presented at the meeting, Dr. Schmajuk of the University of California, San Francisco, and her colleagues looked at 899 new methotrexate users (97% male, mean age 71 years) aged 65 years and older treated at the Veterans Health Administration (VHA) during 2007-2008.

The study was conducted in response to the recent measure issued by the National Quality Forum, which assesses whether rheumatoid arthritis patients prescribed methotrexate received an LFT within 120 days of their prescription claim. The measure is for public quality reporting purposes.

First, Dr. Schmajuk looked at how many patients met the National Quality Forum’s measure.

Patients all had at least a 28-day supply of methotrexate with follow-up at the VHA for 3 months after the drug was dispensed.

Patients were excluded from the study if they had any diagnosis of inflammatory bowel disease or if they sought medical care outside the VHA, and the researchers correlated the first abnormal LFT with the rate of methotrexate discontinuation.

Overall, they found that 148 patients (16.5%) did not have any LFT testing after methotrexate was initiated.

Among the patients who did have their LFTs monitored, 136 (15.1%) had any abnormality of AST or ALT, and only 49 patients (5%) had an elevation of at least 1.5 times the upper limit of normal; among these, methotrexate was discontinued in 27 patients.

However, the researchers also found that methotrexate was discontinued in 28 (32%) of 87 patients with LFT elevations less than 1.5 times the upper limit of normal.

In an e-mail interview, Dr. Schmajuk conceded that a full chart review on these patients has not yet been completed, and that "it is entirely possible that patients were discontinuing [methotrexate] for reasons not related to the LFTs."

However, "We need more research to help decide what a safe cutoff of discontinuation should be – it is possible that it is higher than previously thought."

She added: "In the future, we should be able to tailor monitoring frequency to individual patients."

A second poster, also presented at the meeting, offered a step forward toward just that.

In that study, Dr. Monica Ramirez of Brigham and Women’s Hospital, Boston, attempted to identify clinical predictors of liver enzyme elevation in methotrexate-treated rheumatoid arthritis patients.

Dr. Ramirez and her colleagues conducted detailed chart evaluations of 500 rheumatoid arthritis patients treated at a single center since 1992 who were identified as ever having received treatment with methotrexate and who had LFTs greater than two times the upper limit of normal.

Patients were excluded if they had ever been diagnosed with hepatitis or any other liver disease, or if they had any concurrent hospital or clinic visits for cardiac disease, sepsis, acute kidney disease, metastatic cancer, trauma, or surgery.

A total of 90 (18%) cases were confirmed as having LFT elevations attributed to methotrexate usage.

The authors then assessed the relationship between several known risk factors for liver toxicity to see whether any of them predicted methotrexate dose reduction or discontinuation: age, sex, obesity, hyperlipidemia, methotrexate dose (2.5-7.5 mg, 10-17.5 mg, or 20-25 mg), alcohol use, statin use, and NSAID use.

In univariate analysis, only obesity was significantly associated with a likelihood of methotrexate discontinuation or dose reduction (odds ratio, 2.89; 95% confidence interval, 1.20-7.00; P = .02). Similarly, in multivariate analysis, obesity was the lone predictor (OR, 2.60; 95% CI, 1.01-6.66; P = .05).

"This suggests a potentially heightened risk of hepatotoxicity among obese patients," the authors concluded.

Dr. Schmajuk and her fellow researchers reported no disclosures and no outside funding for their study. The authors of the second study, led by Dr. Ramirez, reported funding from the National Institutes of Health, and one of the investigators reported financial support from Amgen, Abbott, and other companies.

WASHINGTON – The presence of the antisynthetase antibody Jo-1, as well as Mi-2 autoantibodies, strongly predicted improvement in rituximab-treated myositis patients.

On the other hand, global damage is a poor indicator of good response to rituximab in multivariate analysis, meaning that further research into these biomarkers – especially Jo-1 – could have a major impact on treatment in this population, reported Dr. Rohit Aggarwal at the annual meeting of the American College of Rheumatology.

Denise Napoli/IMNG Medical Media

Dr. Aggarwal of the myositis center of the University of Pittsburgh and his colleagues looked at data from the RIM study (Rituximab in Myositis), which evaluated 200 myositis patients treated with the B-cell depleting agent, 83% of whom met the "definition of improvement" (DOI).

The DOI included a 20% or greater improvement in three of six measures: manual muscle testing, muscle enzymes, health assessment questionnaire, patient/parent global assessment, physician global disease activity assessment, and extramuscular disease activity, with not more than 25% worsening of greater than two measures.

These improvements also had to be noted at two consecutive visits to count as meeting the DOI.

Overall, 76 of the 200 myositis patients were more specifically classified as having adult polymyositis; 76 had adult dermatomyositis; and the remaining 48 patients had juvenile dermatomyositis.

In univariate analysis, several factors were associated with more rapid achievement of the DOI. These included lower baseline muscle damage, a higher white blood cell count, lower global damage, and the absence of muscle atrophy.

However, "the primary and strongest predictor of improvement on univariate analysis was autoantibodies," said Dr. Aggarwal – specifically, Jo-1 and Mi-2 – but also other myositis-associated antibodies, including SRP.

Dr. Aggarwal then conducted a multivariate analysis looking only at those variables with P value less than .1 in univariate assessment.

This time, the only significant predictors of improvement were the presence of the antisynthetase autoantibody Jo-1, but only in adults (hazard ratio, 3.08; 95% confidence interval, 1.80-5.28) as well as Mi-2, but only in juvenile and adult dermatomyositis – not adult polymyositis (HR 2.49; 95% CI, 1.42-4.41).

Other antibodies, including those to the signal recognition particle, did not confer a significantly increased association with improvement.

On the other hand, having less global damage at baseline was associated with improvement at 8 weeks, but the effect was washed out by week 20.

"Our findings regarding anti–Jo-1 are even more interesting when these results are coupled with other data that were presented in a concurrent session yesterday," said Dr. Aggarwal, citing a study he also led looking at the relation between anti–Jo-1 serum levels and the six improvement measures assessed in the DOI.

In that study, "After start of the treatment [with rituximab], autoantibody levels in Jo-1 subjects decreased by approximately nine units per week," he wrote.

"Anti–Jo-1 levels longitudinally correlated with all core set measures [of improvement] univariately and after adjusting for IgG levels."

He added, "These data suggest that anti–Jo-1 is also a disease biomarker."

"Further study of B-cell depletion in autoantibody positive, low-damage and juvenile dermatomyositis is warranted."

The RIM study was funded by Genentech, maker of rituximab; several investigators reported relationships to Genentech as well as other pharmaceutical companies.

WASHINGTON – The presence of the antisynthetase antibody Jo-1, as well as Mi-2 autoantibodies, strongly predicted improvement in rituximab-treated myositis patients.

On the other hand, global damage is a poor indicator of good response to rituximab in multivariate analysis, meaning that further research into these biomarkers – especially Jo-1 – could have a major impact on treatment in this population, reported Dr. Rohit Aggarwal at the annual meeting of the American College of Rheumatology.

Denise Napoli/IMNG Medical Media

Dr. Aggarwal of the myositis center of the University of Pittsburgh and his colleagues looked at data from the RIM study (Rituximab in Myositis), which evaluated 200 myositis patients treated with the B-cell depleting agent, 83% of whom met the "definition of improvement" (DOI).

The DOI included a 20% or greater improvement in three of six measures: manual muscle testing, muscle enzymes, health assessment questionnaire, patient/parent global assessment, physician global disease activity assessment, and extramuscular disease activity, with not more than 25% worsening of greater than two measures.

These improvements also had to be noted at two consecutive visits to count as meeting the DOI.

Overall, 76 of the 200 myositis patients were more specifically classified as having adult polymyositis; 76 had adult dermatomyositis; and the remaining 48 patients had juvenile dermatomyositis.

In univariate analysis, several factors were associated with more rapid achievement of the DOI. These included lower baseline muscle damage, a higher white blood cell count, lower global damage, and the absence of muscle atrophy.

However, "the primary and strongest predictor of improvement on univariate analysis was autoantibodies," said Dr. Aggarwal – specifically, Jo-1 and Mi-2 – but also other myositis-associated antibodies, including SRP.

Dr. Aggarwal then conducted a multivariate analysis looking only at those variables with P value less than .1 in univariate assessment.

This time, the only significant predictors of improvement were the presence of the antisynthetase autoantibody Jo-1, but only in adults (hazard ratio, 3.08; 95% confidence interval, 1.80-5.28) as well as Mi-2, but only in juvenile and adult dermatomyositis – not adult polymyositis (HR 2.49; 95% CI, 1.42-4.41).

Other antibodies, including those to the signal recognition particle, did not confer a significantly increased association with improvement.

On the other hand, having less global damage at baseline was associated with improvement at 8 weeks, but the effect was washed out by week 20.

"Our findings regarding anti–Jo-1 are even more interesting when these results are coupled with other data that were presented in a concurrent session yesterday," said Dr. Aggarwal, citing a study he also led looking at the relation between anti–Jo-1 serum levels and the six improvement measures assessed in the DOI.

In that study, "After start of the treatment [with rituximab], autoantibody levels in Jo-1 subjects decreased by approximately nine units per week," he wrote.

"Anti–Jo-1 levels longitudinally correlated with all core set measures [of improvement] univariately and after adjusting for IgG levels."

He added, "These data suggest that anti–Jo-1 is also a disease biomarker."

"Further study of B-cell depletion in autoantibody positive, low-damage and juvenile dermatomyositis is warranted."

The RIM study was funded by Genentech, maker of rituximab; several investigators reported relationships to Genentech as well as other pharmaceutical companies.

WASHINGTON – The presence of the antisynthetase antibody Jo-1, as well as Mi-2 autoantibodies, strongly predicted improvement in rituximab-treated myositis patients.

On the other hand, global damage is a poor indicator of good response to rituximab in multivariate analysis, meaning that further research into these biomarkers – especially Jo-1 – could have a major impact on treatment in this population, reported Dr. Rohit Aggarwal at the annual meeting of the American College of Rheumatology.

Denise Napoli/IMNG Medical Media

Dr. Aggarwal of the myositis center of the University of Pittsburgh and his colleagues looked at data from the RIM study (Rituximab in Myositis), which evaluated 200 myositis patients treated with the B-cell depleting agent, 83% of whom met the "definition of improvement" (DOI).

The DOI included a 20% or greater improvement in three of six measures: manual muscle testing, muscle enzymes, health assessment questionnaire, patient/parent global assessment, physician global disease activity assessment, and extramuscular disease activity, with not more than 25% worsening of greater than two measures.

These improvements also had to be noted at two consecutive visits to count as meeting the DOI.

Overall, 76 of the 200 myositis patients were more specifically classified as having adult polymyositis; 76 had adult dermatomyositis; and the remaining 48 patients had juvenile dermatomyositis.

In univariate analysis, several factors were associated with more rapid achievement of the DOI. These included lower baseline muscle damage, a higher white blood cell count, lower global damage, and the absence of muscle atrophy.

However, "the primary and strongest predictor of improvement on univariate analysis was autoantibodies," said Dr. Aggarwal – specifically, Jo-1 and Mi-2 – but also other myositis-associated antibodies, including SRP.

Dr. Aggarwal then conducted a multivariate analysis looking only at those variables with P value less than .1 in univariate assessment.

This time, the only significant predictors of improvement were the presence of the antisynthetase autoantibody Jo-1, but only in adults (hazard ratio, 3.08; 95% confidence interval, 1.80-5.28) as well as Mi-2, but only in juvenile and adult dermatomyositis – not adult polymyositis (HR 2.49; 95% CI, 1.42-4.41).

Other antibodies, including those to the signal recognition particle, did not confer a significantly increased association with improvement.

On the other hand, having less global damage at baseline was associated with improvement at 8 weeks, but the effect was washed out by week 20.

"Our findings regarding anti–Jo-1 are even more interesting when these results are coupled with other data that were presented in a concurrent session yesterday," said Dr. Aggarwal, citing a study he also led looking at the relation between anti–Jo-1 serum levels and the six improvement measures assessed in the DOI.

In that study, "After start of the treatment [with rituximab], autoantibody levels in Jo-1 subjects decreased by approximately nine units per week," he wrote.

"Anti–Jo-1 levels longitudinally correlated with all core set measures [of improvement] univariately and after adjusting for IgG levels."

He added, "These data suggest that anti–Jo-1 is also a disease biomarker."

"Further study of B-cell depletion in autoantibody positive, low-damage and juvenile dermatomyositis is warranted."

The RIM study was funded by Genentech, maker of rituximab; several investigators reported relationships to Genentech as well as other pharmaceutical companies.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Tocilizumab led to a rapid clinical improvement in polyarticular juvenile idiopathic arthritis that was sustained at 40 weeks.

Moreover, the interleukin-6 (IL-6) receptor inhibitor was relatively safe in this population, with a profile similar to that of other populations treated with tocilizumab, for instance systemic juvenile idiopathic arthritis (JIA) patients. The Food and Drug Administration approved tocilizumab for use in children with systemic JIA in 2011 and a year earlier for use in adults with moderately to severely active RA.

That was the finding from the phase III CHERISH trial presented here by Dr. Hermine Brunner on Nov. 12 at the annual meeting of the American College of Rheumatology.

Dr. Brunner of the Cincinnati Children’s Hospital Medical Center and her colleagues looked at 188 patients aged 2-17 years with active polyarticular JIA.

For the first 16 weeks, all patients received open-label tocilizumab injections every 4 weeks according to body weight, with patients who were at least 30 kg receiving 8 mg/kg (n = 119) and patients less than 30 kg randomized to receive either 8 mg/kg (n = 34) or 10 mg/kg (n = 35).

The primary end point was achievement of a JIA ACR30 response, indicating a 30% improvement from baseline in at least three of six criteria without a worsening of greater than 30% in one remaining measure, including active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level (either erythrocyte sedimentation rate or C-reactive protein).

By the end of the 16 weeks, 93% of the heavier patients (who received 8 mg/kg) had achieved a JIA ACR30 response; 89% of the lighter patients taking 10 mg/kg achieved that level, and 77% of the lighter 8 mg/kg patients.

Moreover, 25% of patients in the heavier group achieved a JIA ACR90 at the end of 16 weeks, as did 31% of the 10 mg/kg lower-weight group and 24% of the 8 mg/kg lower-weight group, reported Dr. Brunner.

At week 16, patients who achieved a JIA-ACR30 response moved on to the second part of the study, a 24-week, double-blind randomization to either placebo or to continue tocilizumab at the same dose.

By week 40, only 54% of placebo patients were at JIA ACR30, compared with 74% of the treatment group (P = .0084).

Moreover, "nearly half" (45%) of the treatment group patients maintained a JIA ACR90 at the end of part two, said Dr. Brunner.

Looking at adverse events, the most commonly reported were infections and infestations, with 164 infections/100-person-years, followed by gastrointestinal disorders, with 71 incidences/100 person-years.

Neutropenia occurred in 3.7% of patients, though Dr. Brunner stated it was "not clearly associated" with any infectious event.

LDL cholesterol levels were elevated to 110 mg/dL or greater in 11.4% of patients, but there were no grade IV lab abnormalities reported, nor were there any deaths in the study.

"The safety profile is quite comparable to what has been seen and reported in other studies" of patients taking tocilizumab, said Dr. Brunner.

However, she added that longer term safety data are forthcoming from this ongoing trial.

Several investigators disclosed multiple relationships to pharmaceutical companies including the maker of tocilizumab, Roche Pharmaceuticals, who also sponsored the study.

WASHINGTON – Tocilizumab led to a rapid clinical improvement in polyarticular juvenile idiopathic arthritis that was sustained at 40 weeks.

Moreover, the interleukin-6 (IL-6) receptor inhibitor was relatively safe in this population, with a profile similar to that of other populations treated with tocilizumab, for instance systemic juvenile idiopathic arthritis (JIA) patients. The Food and Drug Administration approved tocilizumab for use in children with systemic JIA in 2011 and a year earlier for use in adults with moderately to severely active RA.

That was the finding from the phase III CHERISH trial presented here by Dr. Hermine Brunner on Nov. 12 at the annual meeting of the American College of Rheumatology.

Dr. Brunner of the Cincinnati Children’s Hospital Medical Center and her colleagues looked at 188 patients aged 2-17 years with active polyarticular JIA.

For the first 16 weeks, all patients received open-label tocilizumab injections every 4 weeks according to body weight, with patients who were at least 30 kg receiving 8 mg/kg (n = 119) and patients less than 30 kg randomized to receive either 8 mg/kg (n = 34) or 10 mg/kg (n = 35).

The primary end point was achievement of a JIA ACR30 response, indicating a 30% improvement from baseline in at least three of six criteria without a worsening of greater than 30% in one remaining measure, including active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level (either erythrocyte sedimentation rate or C-reactive protein).

By the end of the 16 weeks, 93% of the heavier patients (who received 8 mg/kg) had achieved a JIA ACR30 response; 89% of the lighter patients taking 10 mg/kg achieved that level, and 77% of the lighter 8 mg/kg patients.

Moreover, 25% of patients in the heavier group achieved a JIA ACR90 at the end of 16 weeks, as did 31% of the 10 mg/kg lower-weight group and 24% of the 8 mg/kg lower-weight group, reported Dr. Brunner.

At week 16, patients who achieved a JIA-ACR30 response moved on to the second part of the study, a 24-week, double-blind randomization to either placebo or to continue tocilizumab at the same dose.

By week 40, only 54% of placebo patients were at JIA ACR30, compared with 74% of the treatment group (P = .0084).

Moreover, "nearly half" (45%) of the treatment group patients maintained a JIA ACR90 at the end of part two, said Dr. Brunner.

Looking at adverse events, the most commonly reported were infections and infestations, with 164 infections/100-person-years, followed by gastrointestinal disorders, with 71 incidences/100 person-years.

Neutropenia occurred in 3.7% of patients, though Dr. Brunner stated it was "not clearly associated" with any infectious event.

LDL cholesterol levels were elevated to 110 mg/dL or greater in 11.4% of patients, but there were no grade IV lab abnormalities reported, nor were there any deaths in the study.

"The safety profile is quite comparable to what has been seen and reported in other studies" of patients taking tocilizumab, said Dr. Brunner.

However, she added that longer term safety data are forthcoming from this ongoing trial.

Several investigators disclosed multiple relationships to pharmaceutical companies including the maker of tocilizumab, Roche Pharmaceuticals, who also sponsored the study.

WASHINGTON – Tocilizumab led to a rapid clinical improvement in polyarticular juvenile idiopathic arthritis that was sustained at 40 weeks.

Moreover, the interleukin-6 (IL-6) receptor inhibitor was relatively safe in this population, with a profile similar to that of other populations treated with tocilizumab, for instance systemic juvenile idiopathic arthritis (JIA) patients. The Food and Drug Administration approved tocilizumab for use in children with systemic JIA in 2011 and a year earlier for use in adults with moderately to severely active RA.

That was the finding from the phase III CHERISH trial presented here by Dr. Hermine Brunner on Nov. 12 at the annual meeting of the American College of Rheumatology.

Dr. Brunner of the Cincinnati Children’s Hospital Medical Center and her colleagues looked at 188 patients aged 2-17 years with active polyarticular JIA.

For the first 16 weeks, all patients received open-label tocilizumab injections every 4 weeks according to body weight, with patients who were at least 30 kg receiving 8 mg/kg (n = 119) and patients less than 30 kg randomized to receive either 8 mg/kg (n = 34) or 10 mg/kg (n = 35).

The primary end point was achievement of a JIA ACR30 response, indicating a 30% improvement from baseline in at least three of six criteria without a worsening of greater than 30% in one remaining measure, including active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level (either erythrocyte sedimentation rate or C-reactive protein).

By the end of the 16 weeks, 93% of the heavier patients (who received 8 mg/kg) had achieved a JIA ACR30 response; 89% of the lighter patients taking 10 mg/kg achieved that level, and 77% of the lighter 8 mg/kg patients.

Moreover, 25% of patients in the heavier group achieved a JIA ACR90 at the end of 16 weeks, as did 31% of the 10 mg/kg lower-weight group and 24% of the 8 mg/kg lower-weight group, reported Dr. Brunner.

At week 16, patients who achieved a JIA-ACR30 response moved on to the second part of the study, a 24-week, double-blind randomization to either placebo or to continue tocilizumab at the same dose.

By week 40, only 54% of placebo patients were at JIA ACR30, compared with 74% of the treatment group (P = .0084).

Moreover, "nearly half" (45%) of the treatment group patients maintained a JIA ACR90 at the end of part two, said Dr. Brunner.

Looking at adverse events, the most commonly reported were infections and infestations, with 164 infections/100-person-years, followed by gastrointestinal disorders, with 71 incidences/100 person-years.

Neutropenia occurred in 3.7% of patients, though Dr. Brunner stated it was "not clearly associated" with any infectious event.

LDL cholesterol levels were elevated to 110 mg/dL or greater in 11.4% of patients, but there were no grade IV lab abnormalities reported, nor were there any deaths in the study.

"The safety profile is quite comparable to what has been seen and reported in other studies" of patients taking tocilizumab, said Dr. Brunner.

However, she added that longer term safety data are forthcoming from this ongoing trial.

Several investigators disclosed multiple relationships to pharmaceutical companies including the maker of tocilizumab, Roche Pharmaceuticals, who also sponsored the study.

WASHINGTON – Anti–tumor necrosis factor therapy does not increase the risk of lymphoma in patients with rheumatoid arthritis.

That’s the conclusion of a study presented in a plenary session here by Dr. Kimme L. Hyrich on Monday, Nov. 12, at the annual meeting of the American College of Rheumatology.

"The challenge in studying whether therapies for rheumatoid arthritis (RA) patients can increase the risk of lymphoma is the knowledge that the disease itself has been associated with this outcome," said Dr. Hyrich.

"It’s possible that with immunosuppression, we may see an increased risk of lymphoma, but equally, if we can control the disease activity that has been associated with this outcome, it’s possible that we actually can see a decrease in lymphoma risk over time."

Dr. Hyrich, of the arthritis research UK epidemiology unit at the University of Manchester (England), and colleagues looked at patients from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective registry of RA patients taking biologic drugs, recruited between 2001 and 2009.

The treatment group comprised 11,987 patients who started therapy with an anti–tumor necrosis factor (TNF) including infliximab, etanercept, or adalimumab; they were compared to 3,465 patients who were treated solely with nonbiologic disease modifying antirheumatic drugs (DMARDs).

Incident cancers were detected either by flagging in a national cancer database (95% of cancers were identified by this method, according to Dr. Hyrich) in one of six monthly patient and physician questionnaires, or in annual physician questionnaires thereafter.

Subjects were followed until Sept. 30, 2010, or their first lymphoma, or death, whichever came first.

The cutoff date of the study was 2010 because there can be up to a 2-year lag between incident cancer and reporting of those data in the registry, due to rigorous confirmatory processes, said Dr. Hyrich.

The investigators found 84 incident lymphomas over the study period: 20 in the nonbiologic DMARD patients and 64 in the anti-TNF cohort, for a rate of 152 per 100,000 person years versus 96 per 100,000 person-years, respectively.

The tally included five cases of Hodgkin’s lymphomas in the nonbiologic DMARD group and nine in the anti-TNF patients. Among the non-Hodgkin’s lymphoma cases, diffuse large B cell lymphomas accounted for the greatest proportion of cancers.

After adjustment for baseline age, gender, disease activity score, health assessment questionnaire results, disease duration, smoking, and current or previous cyclophosphamide use, the hazard ratio for all lymphomas for anti-TNF users was calculated to be a nonsignificant 1.13 (95% confidence interval, 0.55-2.31).

Similarly, looking at non-Hodgkin’s lymphoma only, Dr. Hyrich determined an adjusted hazard ratio among the anti-TNF patients of 1.26, also nonsignificant (95% CI, 0.58-2.72).

In her presentation, Dr. Hyrich commented that the study was unable to assess risk associated with a particular anti-TNF agent, given that the majority of patients in this real-world cohort had a history of treatment with multiple drugs in the class; indeed, 15% of the cohort had a history of treatment with three or more anti-TNF agents.

"How do you attribute risk in a situation where patients have been exposed to all of these agents?" she said.

"I think further analysis of these cohorts is needed to know whether any exposure to anti-TNFs, or any particular order of anti-TNFs, or any particular duration of anti-TNFs" increases risk.

The researchers stated that they had no disclosures relative to this presentation.

WASHINGTON – Anti–tumor necrosis factor therapy does not increase the risk of lymphoma in patients with rheumatoid arthritis.

That’s the conclusion of a study presented in a plenary session here by Dr. Kimme L. Hyrich on Monday, Nov. 12, at the annual meeting of the American College of Rheumatology.

"The challenge in studying whether therapies for rheumatoid arthritis (RA) patients can increase the risk of lymphoma is the knowledge that the disease itself has been associated with this outcome," said Dr. Hyrich.

"It’s possible that with immunosuppression, we may see an increased risk of lymphoma, but equally, if we can control the disease activity that has been associated with this outcome, it’s possible that we actually can see a decrease in lymphoma risk over time."

Dr. Hyrich, of the arthritis research UK epidemiology unit at the University of Manchester (England), and colleagues looked at patients from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective registry of RA patients taking biologic drugs, recruited between 2001 and 2009.

The treatment group comprised 11,987 patients who started therapy with an anti–tumor necrosis factor (TNF) including infliximab, etanercept, or adalimumab; they were compared to 3,465 patients who were treated solely with nonbiologic disease modifying antirheumatic drugs (DMARDs).

Incident cancers were detected either by flagging in a national cancer database (95% of cancers were identified by this method, according to Dr. Hyrich) in one of six monthly patient and physician questionnaires, or in annual physician questionnaires thereafter.

Subjects were followed until Sept. 30, 2010, or their first lymphoma, or death, whichever came first.

The cutoff date of the study was 2010 because there can be up to a 2-year lag between incident cancer and reporting of those data in the registry, due to rigorous confirmatory processes, said Dr. Hyrich.

The investigators found 84 incident lymphomas over the study period: 20 in the nonbiologic DMARD patients and 64 in the anti-TNF cohort, for a rate of 152 per 100,000 person years versus 96 per 100,000 person-years, respectively.

The tally included five cases of Hodgkin’s lymphomas in the nonbiologic DMARD group and nine in the anti-TNF patients. Among the non-Hodgkin’s lymphoma cases, diffuse large B cell lymphomas accounted for the greatest proportion of cancers.

After adjustment for baseline age, gender, disease activity score, health assessment questionnaire results, disease duration, smoking, and current or previous cyclophosphamide use, the hazard ratio for all lymphomas for anti-TNF users was calculated to be a nonsignificant 1.13 (95% confidence interval, 0.55-2.31).

Similarly, looking at non-Hodgkin’s lymphoma only, Dr. Hyrich determined an adjusted hazard ratio among the anti-TNF patients of 1.26, also nonsignificant (95% CI, 0.58-2.72).

In her presentation, Dr. Hyrich commented that the study was unable to assess risk associated with a particular anti-TNF agent, given that the majority of patients in this real-world cohort had a history of treatment with multiple drugs in the class; indeed, 15% of the cohort had a history of treatment with three or more anti-TNF agents.

"How do you attribute risk in a situation where patients have been exposed to all of these agents?" she said.

"I think further analysis of these cohorts is needed to know whether any exposure to anti-TNFs, or any particular order of anti-TNFs, or any particular duration of anti-TNFs" increases risk.

The researchers stated that they had no disclosures relative to this presentation.

WASHINGTON – Anti–tumor necrosis factor therapy does not increase the risk of lymphoma in patients with rheumatoid arthritis.

That’s the conclusion of a study presented in a plenary session here by Dr. Kimme L. Hyrich on Monday, Nov. 12, at the annual meeting of the American College of Rheumatology.

"The challenge in studying whether therapies for rheumatoid arthritis (RA) patients can increase the risk of lymphoma is the knowledge that the disease itself has been associated with this outcome," said Dr. Hyrich.

"It’s possible that with immunosuppression, we may see an increased risk of lymphoma, but equally, if we can control the disease activity that has been associated with this outcome, it’s possible that we actually can see a decrease in lymphoma risk over time."

Dr. Hyrich, of the arthritis research UK epidemiology unit at the University of Manchester (England), and colleagues looked at patients from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective registry of RA patients taking biologic drugs, recruited between 2001 and 2009.

The treatment group comprised 11,987 patients who started therapy with an anti–tumor necrosis factor (TNF) including infliximab, etanercept, or adalimumab; they were compared to 3,465 patients who were treated solely with nonbiologic disease modifying antirheumatic drugs (DMARDs).

Incident cancers were detected either by flagging in a national cancer database (95% of cancers were identified by this method, according to Dr. Hyrich) in one of six monthly patient and physician questionnaires, or in annual physician questionnaires thereafter.

Subjects were followed until Sept. 30, 2010, or their first lymphoma, or death, whichever came first.

The cutoff date of the study was 2010 because there can be up to a 2-year lag between incident cancer and reporting of those data in the registry, due to rigorous confirmatory processes, said Dr. Hyrich.

The investigators found 84 incident lymphomas over the study period: 20 in the nonbiologic DMARD patients and 64 in the anti-TNF cohort, for a rate of 152 per 100,000 person years versus 96 per 100,000 person-years, respectively.

The tally included five cases of Hodgkin’s lymphomas in the nonbiologic DMARD group and nine in the anti-TNF patients. Among the non-Hodgkin’s lymphoma cases, diffuse large B cell lymphomas accounted for the greatest proportion of cancers.

After adjustment for baseline age, gender, disease activity score, health assessment questionnaire results, disease duration, smoking, and current or previous cyclophosphamide use, the hazard ratio for all lymphomas for anti-TNF users was calculated to be a nonsignificant 1.13 (95% confidence interval, 0.55-2.31).

Similarly, looking at non-Hodgkin’s lymphoma only, Dr. Hyrich determined an adjusted hazard ratio among the anti-TNF patients of 1.26, also nonsignificant (95% CI, 0.58-2.72).

In her presentation, Dr. Hyrich commented that the study was unable to assess risk associated with a particular anti-TNF agent, given that the majority of patients in this real-world cohort had a history of treatment with multiple drugs in the class; indeed, 15% of the cohort had a history of treatment with three or more anti-TNF agents.

"How do you attribute risk in a situation where patients have been exposed to all of these agents?" she said.

"I think further analysis of these cohorts is needed to know whether any exposure to anti-TNFs, or any particular order of anti-TNFs, or any particular duration of anti-TNFs" increases risk.

The researchers stated that they had no disclosures relative to this presentation.

WASHINGTON – More than one-third of U.S. rheumatoid arthritis patients report using alternative medicine, such as fish oil and glucosamine, at some time after their diagnosis.

However, only 10% of these patients stick with these complementary and alternative (CAM) therapies long term, Dr. Peri H. Pepmueller reported in a poster presentation at the annual meeting of the American College of Rheumatology.

This finding means that rheumatologists "need to ask" about the use of these alternative medicines, Dr. Pepmueller said in an interview.

"I think we can counsel patients that if they want to take them, [they should] take them in addition to the prescription medications," she said.

Dr. Pepmueller of St. Louis University and her colleagues looked at data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry, a multicenter, longitudinal prospective database in the United States with more than 30,000 patients.

The researchers assessed reported CAM use, including the use of fish oil and glucosamine/chondroitin supplements. They also assessed the use of borage seed oil, evening primrose oil, and flax seed oil, the presumed effect of which is to decrease inflammation, Dr. Pepmueller said.

"The oils ... have been shown in many studies to have an anti-inflammatory effect on a variety of chronic conditions in which inflammation is thought to play a role," she said.

In total, 11,970 patients were included in the final analysis. All had at least 2 years of follow-up and at least three visits.

The researchers defined the use of CAM as the use of any of the above-listed therapies within 2 years of their first recorded visit. "Long-term" therapy was defined as the use of the same therapy at either three consecutive visits or all visits in 1 year.

They found that 35.2% of patients reported using one of the complementary therapies looked at, but only 10.8% reported long-term use.

Fish oil was the most commonly reported supplement, used by 27.3% of the cohort.

The next most common supplement was glucosamine/chondroitin, used by a reported 13.6% of the cohort, followed by flax seed oil (3.3%), evening primrose oil (2.1%), and borage seed oil (1.4%).

Dr. Pepmueller then analyzed which, if any, demographic and disease factors predicted complementary alternative medicine use.

Of current smokers, the odds that they would ever use CAM were 0.70 (95% confidence interval, 0.62-0.79; P less than .0001) and the odds of long term CAM use was .71 (95% CI, 0.57-0.87; P less than .05), based on findings of the multivariate analysis.

Patients with education levels of high school or less were also less likely to try complementary medicines, with an OR of 0.69 ( 95% CI, 0.63-0.75; P less than .0001), versus patients with any college-level education.

Geographically, patients in the Western United States were more likely to try complementary medicine alternatives, compared with Midwestern patients (OR, 1.49; 95% CI, 1.29-1.72; P less than .0001), while patients in the Northeastern United States were even less likely than their Midwestern counterparts to try these alternatives (OR, 0.83; 95% CI, 0.74-0.93; P less than .0001 for both values).

On the other hand, while disease duration and severity were not significant predictors of complementary medicine use in a multivariate analysis, unadjusted models showed that a longer duration and a greater number of swollen and tender joints, as well as patient- and physician-assessed disease severity, were all associated with decreased use of complementary medicine.

Dr. Pepmueller also pointed to articles detailing some of the risks involved with alternative medicines, including reports of increased levels of low-density lipoprotein cholesterol levels with fish oil consumption (Rheum. Dis. Clin. North Am. 2011;37:77-84).

Medication interactions are also possible. For example, there have been reports of fish oil potentiating the effects of coumadin.

Dr. Pepmueller stated that she had no relevant financial disclosures; a coinvestigator reported funding from Axio Research.

WASHINGTON – More than one-third of U.S. rheumatoid arthritis patients report using alternative medicine, such as fish oil and glucosamine, at some time after their diagnosis.

However, only 10% of these patients stick with these complementary and alternative (CAM) therapies long term, Dr. Peri H. Pepmueller reported in a poster presentation at the annual meeting of the American College of Rheumatology.

This finding means that rheumatologists "need to ask" about the use of these alternative medicines, Dr. Pepmueller said in an interview.

"I think we can counsel patients that if they want to take them, [they should] take them in addition to the prescription medications," she said.

Dr. Pepmueller of St. Louis University and her colleagues looked at data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry, a multicenter, longitudinal prospective database in the United States with more than 30,000 patients.

The researchers assessed reported CAM use, including the use of fish oil and glucosamine/chondroitin supplements. They also assessed the use of borage seed oil, evening primrose oil, and flax seed oil, the presumed effect of which is to decrease inflammation, Dr. Pepmueller said.

"The oils ... have been shown in many studies to have an anti-inflammatory effect on a variety of chronic conditions in which inflammation is thought to play a role," she said.

In total, 11,970 patients were included in the final analysis. All had at least 2 years of follow-up and at least three visits.

The researchers defined the use of CAM as the use of any of the above-listed therapies within 2 years of their first recorded visit. "Long-term" therapy was defined as the use of the same therapy at either three consecutive visits or all visits in 1 year.

They found that 35.2% of patients reported using one of the complementary therapies looked at, but only 10.8% reported long-term use.

Fish oil was the most commonly reported supplement, used by 27.3% of the cohort.

The next most common supplement was glucosamine/chondroitin, used by a reported 13.6% of the cohort, followed by flax seed oil (3.3%), evening primrose oil (2.1%), and borage seed oil (1.4%).

Dr. Pepmueller then analyzed which, if any, demographic and disease factors predicted complementary alternative medicine use.

Of current smokers, the odds that they would ever use CAM were 0.70 (95% confidence interval, 0.62-0.79; P less than .0001) and the odds of long term CAM use was .71 (95% CI, 0.57-0.87; P less than .05), based on findings of the multivariate analysis.

Patients with education levels of high school or less were also less likely to try complementary medicines, with an OR of 0.69 ( 95% CI, 0.63-0.75; P less than .0001), versus patients with any college-level education.

Geographically, patients in the Western United States were more likely to try complementary medicine alternatives, compared with Midwestern patients (OR, 1.49; 95% CI, 1.29-1.72; P less than .0001), while patients in the Northeastern United States were even less likely than their Midwestern counterparts to try these alternatives (OR, 0.83; 95% CI, 0.74-0.93; P less than .0001 for both values).

On the other hand, while disease duration and severity were not significant predictors of complementary medicine use in a multivariate analysis, unadjusted models showed that a longer duration and a greater number of swollen and tender joints, as well as patient- and physician-assessed disease severity, were all associated with decreased use of complementary medicine.

Dr. Pepmueller also pointed to articles detailing some of the risks involved with alternative medicines, including reports of increased levels of low-density lipoprotein cholesterol levels with fish oil consumption (Rheum. Dis. Clin. North Am. 2011;37:77-84).

Medication interactions are also possible. For example, there have been reports of fish oil potentiating the effects of coumadin.

Dr. Pepmueller stated that she had no relevant financial disclosures; a coinvestigator reported funding from Axio Research.

WASHINGTON – More than one-third of U.S. rheumatoid arthritis patients report using alternative medicine, such as fish oil and glucosamine, at some time after their diagnosis.

However, only 10% of these patients stick with these complementary and alternative (CAM) therapies long term, Dr. Peri H. Pepmueller reported in a poster presentation at the annual meeting of the American College of Rheumatology.

This finding means that rheumatologists "need to ask" about the use of these alternative medicines, Dr. Pepmueller said in an interview.

"I think we can counsel patients that if they want to take them, [they should] take them in addition to the prescription medications," she said.

Dr. Pepmueller of St. Louis University and her colleagues looked at data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry, a multicenter, longitudinal prospective database in the United States with more than 30,000 patients.

The researchers assessed reported CAM use, including the use of fish oil and glucosamine/chondroitin supplements. They also assessed the use of borage seed oil, evening primrose oil, and flax seed oil, the presumed effect of which is to decrease inflammation, Dr. Pepmueller said.

"The oils ... have been shown in many studies to have an anti-inflammatory effect on a variety of chronic conditions in which inflammation is thought to play a role," she said.

In total, 11,970 patients were included in the final analysis. All had at least 2 years of follow-up and at least three visits.

The researchers defined the use of CAM as the use of any of the above-listed therapies within 2 years of their first recorded visit. "Long-term" therapy was defined as the use of the same therapy at either three consecutive visits or all visits in 1 year.

They found that 35.2% of patients reported using one of the complementary therapies looked at, but only 10.8% reported long-term use.

Fish oil was the most commonly reported supplement, used by 27.3% of the cohort.

The next most common supplement was glucosamine/chondroitin, used by a reported 13.6% of the cohort, followed by flax seed oil (3.3%), evening primrose oil (2.1%), and borage seed oil (1.4%).

Dr. Pepmueller then analyzed which, if any, demographic and disease factors predicted complementary alternative medicine use.

Of current smokers, the odds that they would ever use CAM were 0.70 (95% confidence interval, 0.62-0.79; P less than .0001) and the odds of long term CAM use was .71 (95% CI, 0.57-0.87; P less than .05), based on findings of the multivariate analysis.

Patients with education levels of high school or less were also less likely to try complementary medicines, with an OR of 0.69 ( 95% CI, 0.63-0.75; P less than .0001), versus patients with any college-level education.

Geographically, patients in the Western United States were more likely to try complementary medicine alternatives, compared with Midwestern patients (OR, 1.49; 95% CI, 1.29-1.72; P less than .0001), while patients in the Northeastern United States were even less likely than their Midwestern counterparts to try these alternatives (OR, 0.83; 95% CI, 0.74-0.93; P less than .0001 for both values).

On the other hand, while disease duration and severity were not significant predictors of complementary medicine use in a multivariate analysis, unadjusted models showed that a longer duration and a greater number of swollen and tender joints, as well as patient- and physician-assessed disease severity, were all associated with decreased use of complementary medicine.

Dr. Pepmueller also pointed to articles detailing some of the risks involved with alternative medicines, including reports of increased levels of low-density lipoprotein cholesterol levels with fish oil consumption (Rheum. Dis. Clin. North Am. 2011;37:77-84).

Medication interactions are also possible. For example, there have been reports of fish oil potentiating the effects of coumadin.

Dr. Pepmueller stated that she had no relevant financial disclosures; a coinvestigator reported funding from Axio Research.

WASHINGTON – Use of adalimumab in combination with another drug, usually methotrexate, seems to boost treatment response to such an extent that patients with rheumatoid arthritis can sometimes be tapered off one or both drugs over the subsequent 2 years.

Those are the findings of three separate posters that were based on data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry – a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients.

The studies were presented on Nov. 11 at the annual meeting of the American College of Rheumatology.

In the first study, led by Dr. Daniel E. Furst, Carl M. Pearson Professor of Medicine at the University of California, Los Angeles, the researchers looked at RA patients enrolled in CORRONA between March 2002 and September 2011 who initiated adalimumab treatment and had at least one follow-up visit on record.

The researchers assessed 417 patients with 2 years of follow-up, a mean age of 54.2 years, and a mean disease duration of 10.1 years; most (79.3%) were female.

Overall, 67% of patients were treated concurrently with methotrexate upon adalimumab initiation, but at 2 years, the odds ratio for concomitant methotrexate was 0.68 (95% confidence interval, 0.48-0.95; P = .05).

Patients with two or more comorbidities, including hypertension, cancer, chronic obstructive pulmonary disease, and diabetes, were even less likely to continue to need to take methotrexate (OR, 0.48; 95% CI, 0.29-0.80; P = .01).

"This suggests the clinical efficacy of adalimumab in RA disease control across a medically diverse patient population," noted Dr. Furst.

In a second, independent study from CORRONA, Dr. Allan Gibofsky, professor of medicine and public health at Cornell University and professor of law at Fordham University, both in New York, looked at 1,639 patients who initiated adalimumab therapy over the same time period and who had at least one follow-up visit on record.

Dr. Gibofsky found that 1,003 of these patients eventually discontinued adalimumab after a median of 632 days, according to a Kaplan-Meier estimate; 1,358 experienced some form of treatment change (including discontinuation, but also dosing/frequency changes or addition of another disease-modifying antirheumatic drug).

In this analysis, while use of a prior biologic was highly predictive of regimen change (hazard ratio, 1.532; CI, 1.259-1.864; P less than .0001), use of methotrexate at adalimumab initiation was associated with a significantly decreased likelihood of adalimumab treatment change (HR, 0.88; CI, 0.835-0.919; P less than .0001).

Finally, a third CORRONA-based study presented at the meeting confirmed that combination therapy with methotrexate and tumor necrosis factor–inhibitors like adalimumab is increasing.

Dr. Deborah Wenkert of Amgen Inc., based in Thousand Oaks, Calif., and her colleagues looked at the prevalence of combination therapy over two time periods: 2002-2004 and 2007-2009.

She found that the mean clinical disease activity index (CDAI) at initiation of combination therapy was significantly lower during the later time period, versus the earlier, and that "among all RA patients with 2 years of follow-up, a higher percentage of patients initiated combination therapy in 2007-2009 than 2002-2004 in each maximum CDAI category."

The trend could reflect "stricter definition and implementation of aggressive treatment goals in the later time periods," Dr. Wenkert added.

All investigators disclosed multiple relationships to pharmaceutical makers, including the makers of adalimumab.

WASHINGTON – Use of adalimumab in combination with another drug, usually methotrexate, seems to boost treatment response to such an extent that patients with rheumatoid arthritis can sometimes be tapered off one or both drugs over the subsequent 2 years.

Those are the findings of three separate posters that were based on data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry – a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients.

The studies were presented on Nov. 11 at the annual meeting of the American College of Rheumatology.

In the first study, led by Dr. Daniel E. Furst, Carl M. Pearson Professor of Medicine at the University of California, Los Angeles, the researchers looked at RA patients enrolled in CORRONA between March 2002 and September 2011 who initiated adalimumab treatment and had at least one follow-up visit on record.

The researchers assessed 417 patients with 2 years of follow-up, a mean age of 54.2 years, and a mean disease duration of 10.1 years; most (79.3%) were female.

Overall, 67% of patients were treated concurrently with methotrexate upon adalimumab initiation, but at 2 years, the odds ratio for concomitant methotrexate was 0.68 (95% confidence interval, 0.48-0.95; P = .05).

Patients with two or more comorbidities, including hypertension, cancer, chronic obstructive pulmonary disease, and diabetes, were even less likely to continue to need to take methotrexate (OR, 0.48; 95% CI, 0.29-0.80; P = .01).

"This suggests the clinical efficacy of adalimumab in RA disease control across a medically diverse patient population," noted Dr. Furst.

In a second, independent study from CORRONA, Dr. Allan Gibofsky, professor of medicine and public health at Cornell University and professor of law at Fordham University, both in New York, looked at 1,639 patients who initiated adalimumab therapy over the same time period and who had at least one follow-up visit on record.

Dr. Gibofsky found that 1,003 of these patients eventually discontinued adalimumab after a median of 632 days, according to a Kaplan-Meier estimate; 1,358 experienced some form of treatment change (including discontinuation, but also dosing/frequency changes or addition of another disease-modifying antirheumatic drug).

In this analysis, while use of a prior biologic was highly predictive of regimen change (hazard ratio, 1.532; CI, 1.259-1.864; P less than .0001), use of methotrexate at adalimumab initiation was associated with a significantly decreased likelihood of adalimumab treatment change (HR, 0.88; CI, 0.835-0.919; P less than .0001).

Finally, a third CORRONA-based study presented at the meeting confirmed that combination therapy with methotrexate and tumor necrosis factor–inhibitors like adalimumab is increasing.

Dr. Deborah Wenkert of Amgen Inc., based in Thousand Oaks, Calif., and her colleagues looked at the prevalence of combination therapy over two time periods: 2002-2004 and 2007-2009.

She found that the mean clinical disease activity index (CDAI) at initiation of combination therapy was significantly lower during the later time period, versus the earlier, and that "among all RA patients with 2 years of follow-up, a higher percentage of patients initiated combination therapy in 2007-2009 than 2002-2004 in each maximum CDAI category."

The trend could reflect "stricter definition and implementation of aggressive treatment goals in the later time periods," Dr. Wenkert added.

All investigators disclosed multiple relationships to pharmaceutical makers, including the makers of adalimumab.

WASHINGTON – Use of adalimumab in combination with another drug, usually methotrexate, seems to boost treatment response to such an extent that patients with rheumatoid arthritis can sometimes be tapered off one or both drugs over the subsequent 2 years.

Those are the findings of three separate posters that were based on data from the CORRONA (Consortium of Rheumatology Researchers of North America) registry – a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients.

The studies were presented on Nov. 11 at the annual meeting of the American College of Rheumatology.

In the first study, led by Dr. Daniel E. Furst, Carl M. Pearson Professor of Medicine at the University of California, Los Angeles, the researchers looked at RA patients enrolled in CORRONA between March 2002 and September 2011 who initiated adalimumab treatment and had at least one follow-up visit on record.

The researchers assessed 417 patients with 2 years of follow-up, a mean age of 54.2 years, and a mean disease duration of 10.1 years; most (79.3%) were female.

Overall, 67% of patients were treated concurrently with methotrexate upon adalimumab initiation, but at 2 years, the odds ratio for concomitant methotrexate was 0.68 (95% confidence interval, 0.48-0.95; P = .05).

Patients with two or more comorbidities, including hypertension, cancer, chronic obstructive pulmonary disease, and diabetes, were even less likely to continue to need to take methotrexate (OR, 0.48; 95% CI, 0.29-0.80; P = .01).

"This suggests the clinical efficacy of adalimumab in RA disease control across a medically diverse patient population," noted Dr. Furst.

In a second, independent study from CORRONA, Dr. Allan Gibofsky, professor of medicine and public health at Cornell University and professor of law at Fordham University, both in New York, looked at 1,639 patients who initiated adalimumab therapy over the same time period and who had at least one follow-up visit on record.

Dr. Gibofsky found that 1,003 of these patients eventually discontinued adalimumab after a median of 632 days, according to a Kaplan-Meier estimate; 1,358 experienced some form of treatment change (including discontinuation, but also dosing/frequency changes or addition of another disease-modifying antirheumatic drug).

In this analysis, while use of a prior biologic was highly predictive of regimen change (hazard ratio, 1.532; CI, 1.259-1.864; P less than .0001), use of methotrexate at adalimumab initiation was associated with a significantly decreased likelihood of adalimumab treatment change (HR, 0.88; CI, 0.835-0.919; P less than .0001).

Finally, a third CORRONA-based study presented at the meeting confirmed that combination therapy with methotrexate and tumor necrosis factor–inhibitors like adalimumab is increasing.

Dr. Deborah Wenkert of Amgen Inc., based in Thousand Oaks, Calif., and her colleagues looked at the prevalence of combination therapy over two time periods: 2002-2004 and 2007-2009.

She found that the mean clinical disease activity index (CDAI) at initiation of combination therapy was significantly lower during the later time period, versus the earlier, and that "among all RA patients with 2 years of follow-up, a higher percentage of patients initiated combination therapy in 2007-2009 than 2002-2004 in each maximum CDAI category."

The trend could reflect "stricter definition and implementation of aggressive treatment goals in the later time periods," Dr. Wenkert added.

All investigators disclosed multiple relationships to pharmaceutical makers, including the makers of adalimumab.

Increased calcium intake is associated with a reduced risk for primary hyperparathyroidism in women, according to an analysis of data from the Nurses’ Health Study published on Oct. 18.

In what the researchers called the first prospective study to assess the link between hyperparathyroidism and calcium intake, Dr. Julie M. Paik of Brigham and Women’s Hospital in Boston and her colleagues looked at 58,354 women from the Nurses’ Health Study I, an ongoing, prospective cohort study that began in 1976. Participants in the study complete questionnaires every 2 years.

Dietary intake was assessed using the food frequency questionnaire, which asked about participants’ average intake of more than 130 individual food items and 22 beverages during the previous year.

The survey also asked about calcium supplements, vitamin D supplements, and multivitamins, with calcium intake determined by the brand, type, and frequency of use.

Only cases of primary hyperparathyroidism diagnosed between the date on which the 1986 questionnaire was returned and May 31, 2008, were included in the study.

Overall, during 1,475,978 person-years of follow-up, there were 277 cases of incident primary hyperparathyroidism.

After the data were adjusted for age, women in the highest quintile of dietary intake had a relative risk for developing hyperparathyroidism of 0.61, compared with women in the lowest quintile (95% confidence interval, 0.42-0.90; P = .03), the investigators reported (BMJ 2012;345:e6390).

Further adjustments for body mass index, race, smoking, calcium supplement use, intake of vitamin D, dietary intake of vitamin A and protein, alcohol intake, and diuretic use only strengthened the effect: The relative risk among the highest quintile of intake was 0.56, by this calculation, compared with patients in the lowest intake category (95% CI, 0.37-0.86; P = .009).

The authors also looked at supplemental calcium intake, although "because of an insufficient number of cases of primary hyperparathyroidism among the different categories of supplemental calcium use in the earlier time periods, our analysis on the relation between supplemental calcium intake and primary hyperparathyroidism began in 1994 with follow-up until 2008," wrote Dr. Paik and her coinvestigators.

In this analysis, which included 985,628 person-years of follow-up, there were a total of 257 cases of incident primary hyperparathyroidism.

When the findings were adjusted for age, "the relative risk for women taking more than 500 mg/day of calcium supplements compared with those not taking calcium supplements was 0.69 (95% CI, 0.50-0.94; P less than .001)," wrote the authors.

As with dietary intake, the protective effect was only strengthened in multivariable analysis, including adjustment for dietary calcium: The higher-intake group’s risk was 0.41, compared with the lower-intake group (95% CI, 0.29-0.60; P less than .001).

The authors conceded that the study population was exclusively female and almost entirely white, making the findings not necessarily generalizable to men or to women of other races.

Additionally, "although the food frequency questionnaires have been well validated, calcium intake was not perfectly assessed in this study," they wrote.

"However, because of the prospective design, any misclassification would be random with respect to case status, and therefore would probably underestimate the magnitude of the inverse association between calcium intake and risk of primary hyperparathyroidism."

The study investigators stated that they had no relevant financial disclosures. The study was supported by grants from the National Institutes of Health.

Increased calcium intake is associated with a reduced risk for primary hyperparathyroidism in women, according to an analysis of data from the Nurses’ Health Study published on Oct. 18.

In what the researchers called the first prospective study to assess the link between hyperparathyroidism and calcium intake, Dr. Julie M. Paik of Brigham and Women’s Hospital in Boston and her colleagues looked at 58,354 women from the Nurses’ Health Study I, an ongoing, prospective cohort study that began in 1976. Participants in the study complete questionnaires every 2 years.

Dietary intake was assessed using the food frequency questionnaire, which asked about participants’ average intake of more than 130 individual food items and 22 beverages during the previous year.

The survey also asked about calcium supplements, vitamin D supplements, and multivitamins, with calcium intake determined by the brand, type, and frequency of use.

Only cases of primary hyperparathyroidism diagnosed between the date on which the 1986 questionnaire was returned and May 31, 2008, were included in the study.

Overall, during 1,475,978 person-years of follow-up, there were 277 cases of incident primary hyperparathyroidism.

After the data were adjusted for age, women in the highest quintile of dietary intake had a relative risk for developing hyperparathyroidism of 0.61, compared with women in the lowest quintile (95% confidence interval, 0.42-0.90; P = .03), the investigators reported (BMJ 2012;345:e6390).

Further adjustments for body mass index, race, smoking, calcium supplement use, intake of vitamin D, dietary intake of vitamin A and protein, alcohol intake, and diuretic use only strengthened the effect: The relative risk among the highest quintile of intake was 0.56, by this calculation, compared with patients in the lowest intake category (95% CI, 0.37-0.86; P = .009).

The authors also looked at supplemental calcium intake, although "because of an insufficient number of cases of primary hyperparathyroidism among the different categories of supplemental calcium use in the earlier time periods, our analysis on the relation between supplemental calcium intake and primary hyperparathyroidism began in 1994 with follow-up until 2008," wrote Dr. Paik and her coinvestigators.

In this analysis, which included 985,628 person-years of follow-up, there were a total of 257 cases of incident primary hyperparathyroidism.

When the findings were adjusted for age, "the relative risk for women taking more than 500 mg/day of calcium supplements compared with those not taking calcium supplements was 0.69 (95% CI, 0.50-0.94; P less than .001)," wrote the authors.

As with dietary intake, the protective effect was only strengthened in multivariable analysis, including adjustment for dietary calcium: The higher-intake group’s risk was 0.41, compared with the lower-intake group (95% CI, 0.29-0.60; P less than .001).

The authors conceded that the study population was exclusively female and almost entirely white, making the findings not necessarily generalizable to men or to women of other races.

Additionally, "although the food frequency questionnaires have been well validated, calcium intake was not perfectly assessed in this study," they wrote.

"However, because of the prospective design, any misclassification would be random with respect to case status, and therefore would probably underestimate the magnitude of the inverse association between calcium intake and risk of primary hyperparathyroidism."

The study investigators stated that they had no relevant financial disclosures. The study was supported by grants from the National Institutes of Health.

Increased calcium intake is associated with a reduced risk for primary hyperparathyroidism in women, according to an analysis of data from the Nurses’ Health Study published on Oct. 18.

In what the researchers called the first prospective study to assess the link between hyperparathyroidism and calcium intake, Dr. Julie M. Paik of Brigham and Women’s Hospital in Boston and her colleagues looked at 58,354 women from the Nurses’ Health Study I, an ongoing, prospective cohort study that began in 1976. Participants in the study complete questionnaires every 2 years.

Dietary intake was assessed using the food frequency questionnaire, which asked about participants’ average intake of more than 130 individual food items and 22 beverages during the previous year.

The survey also asked about calcium supplements, vitamin D supplements, and multivitamins, with calcium intake determined by the brand, type, and frequency of use.

Only cases of primary hyperparathyroidism diagnosed between the date on which the 1986 questionnaire was returned and May 31, 2008, were included in the study.

Overall, during 1,475,978 person-years of follow-up, there were 277 cases of incident primary hyperparathyroidism.

After the data were adjusted for age, women in the highest quintile of dietary intake had a relative risk for developing hyperparathyroidism of 0.61, compared with women in the lowest quintile (95% confidence interval, 0.42-0.90; P = .03), the investigators reported (BMJ 2012;345:e6390).

Further adjustments for body mass index, race, smoking, calcium supplement use, intake of vitamin D, dietary intake of vitamin A and protein, alcohol intake, and diuretic use only strengthened the effect: The relative risk among the highest quintile of intake was 0.56, by this calculation, compared with patients in the lowest intake category (95% CI, 0.37-0.86; P = .009).

The authors also looked at supplemental calcium intake, although "because of an insufficient number of cases of primary hyperparathyroidism among the different categories of supplemental calcium use in the earlier time periods, our analysis on the relation between supplemental calcium intake and primary hyperparathyroidism began in 1994 with follow-up until 2008," wrote Dr. Paik and her coinvestigators.

In this analysis, which included 985,628 person-years of follow-up, there were a total of 257 cases of incident primary hyperparathyroidism.

When the findings were adjusted for age, "the relative risk for women taking more than 500 mg/day of calcium supplements compared with those not taking calcium supplements was 0.69 (95% CI, 0.50-0.94; P less than .001)," wrote the authors.

As with dietary intake, the protective effect was only strengthened in multivariable analysis, including adjustment for dietary calcium: The higher-intake group’s risk was 0.41, compared with the lower-intake group (95% CI, 0.29-0.60; P less than .001).

The authors conceded that the study population was exclusively female and almost entirely white, making the findings not necessarily generalizable to men or to women of other races.

Additionally, "although the food frequency questionnaires have been well validated, calcium intake was not perfectly assessed in this study," they wrote.

"However, because of the prospective design, any misclassification would be random with respect to case status, and therefore would probably underestimate the magnitude of the inverse association between calcium intake and risk of primary hyperparathyroidism."

The study investigators stated that they had no relevant financial disclosures. The study was supported by grants from the National Institutes of Health.