Mitchel L. Zoler, PhD

BERLIN – The 2010 criteria for classifying rheumatoid arthritis accomplish what they were designed to do in patients with early disease: boost the sensitivity for identifying patients who are likely to eventually develop rheumatoid arthritis and could therefore benefit from early treatment.

A comparison of the 2010 criteria (Arthritis Rheum. 2010;62:2569-81) against the 1987 rheumatoid arthritis (RA) classification criteria (Arthritis Rheum.1987;31:315-24) in a cohort of 269 patients with early disease showed that the 2010 method increased the sensitivity for finding patients with early-stage disease who were destined eventually to develop full-blown RA over the next 6 years to 86% sensitivity, compared with 78% sensitivity for the 1987 criteria, a statistically significant difference, Dr. Julia Nicolau said at the annual meeting of the European Congress of Rheumatology.

Among the 229 patients from this group with no joint erosions detectable at baseline, the 2010 criteria worked even better, primarily because the specificity of the criteria jumped from 59% in the full cohort examined to 71% when patients with one or more joint erosions were excluded. The positive predictive value of the 2010 criteria was 80% for the entire group of 269 (compared with 81% for the 1987 criteria), but in the subgroup without erosions, the positive predictive value of the 2010 criteria was 85%, said Dr. Nicolau, a rheumatologist at Rouen (France) University Hospital.

In addition, in an analysis of the area under the receiver-operator curve the 2010 criteria applied to patients without any erosions at baseline accounted for 82% of the confirmed RA cases after 6 years, significantly more than the 79% of cases identified by the 1987 criteria.

"The mind-set we had when we set up the [2010] criteria was to try to catch everybody [who would soon develop RA], and accept that we might treat some people who we don’t know will develop erosive disease," said Dr. Alan J. Silman, medical director of the U.K. Arthritis Research Campaign and a member of the committee that wrote the 2010 RA classification criteria. "Missing a case of RA is problematic because the interventions we have are fairly effective. Among patients with early arthritis, some will progress to persistent, erosive disease, and the issue is what should we use to identify the patients who should receive intervention" at an early stage. "We may treat some patients who won’t have bad outcomes [and won’t progress to erosive joints], but we accept that we need to treat a lot of patients to prevent the bad outcomes."

The results reported by Dr. Nicolau used the Very Early Arthritis Cohort, which included 269 patients with at least two swollen joints for less than 6 months who appeared to have no other type of arthritis causing their symptoms. The 2010 criteria identified 68% as having RA, while the 1987 criteria identified 59% of these early-stage patients with RA. The researchers had 6-year follow-up data for these patients, which allowed them to compare the results of baseline assessment with each of the two criteria against the eventual, long-term clinical diagnosis of RA.

Dr. Nicolau and her associates also evaluated the 1987 and 2010 criteria using a different end point as the standard for determining which patients eventually developed RA, the number of patients with at least three erosive joints after 2 years of follow-up. Against this standard, the 2010 criteria performed virtually identically as the 1987 criteria. Both criteria identified early-stage RA with 95% sensitivity, and both accounted for 82% of early-stage patients who eventually developed RA 2 years later.

Dr. Nicolau and Dr. Silman said that they had no disclosures. Dr. Silman was a member of the committee that wrote the 2010 rheumatoid arthritis classification criteria.

BERLIN – The 2010 criteria for classifying rheumatoid arthritis accomplish what they were designed to do in patients with early disease: boost the sensitivity for identifying patients who are likely to eventually develop rheumatoid arthritis and could therefore benefit from early treatment.

A comparison of the 2010 criteria (Arthritis Rheum. 2010;62:2569-81) against the 1987 rheumatoid arthritis (RA) classification criteria (Arthritis Rheum.1987;31:315-24) in a cohort of 269 patients with early disease showed that the 2010 method increased the sensitivity for finding patients with early-stage disease who were destined eventually to develop full-blown RA over the next 6 years to 86% sensitivity, compared with 78% sensitivity for the 1987 criteria, a statistically significant difference, Dr. Julia Nicolau said at the annual meeting of the European Congress of Rheumatology.

Among the 229 patients from this group with no joint erosions detectable at baseline, the 2010 criteria worked even better, primarily because the specificity of the criteria jumped from 59% in the full cohort examined to 71% when patients with one or more joint erosions were excluded. The positive predictive value of the 2010 criteria was 80% for the entire group of 269 (compared with 81% for the 1987 criteria), but in the subgroup without erosions, the positive predictive value of the 2010 criteria was 85%, said Dr. Nicolau, a rheumatologist at Rouen (France) University Hospital.

In addition, in an analysis of the area under the receiver-operator curve the 2010 criteria applied to patients without any erosions at baseline accounted for 82% of the confirmed RA cases after 6 years, significantly more than the 79% of cases identified by the 1987 criteria.

"The mind-set we had when we set up the [2010] criteria was to try to catch everybody [who would soon develop RA], and accept that we might treat some people who we don’t know will develop erosive disease," said Dr. Alan J. Silman, medical director of the U.K. Arthritis Research Campaign and a member of the committee that wrote the 2010 RA classification criteria. "Missing a case of RA is problematic because the interventions we have are fairly effective. Among patients with early arthritis, some will progress to persistent, erosive disease, and the issue is what should we use to identify the patients who should receive intervention" at an early stage. "We may treat some patients who won’t have bad outcomes [and won’t progress to erosive joints], but we accept that we need to treat a lot of patients to prevent the bad outcomes."

The results reported by Dr. Nicolau used the Very Early Arthritis Cohort, which included 269 patients with at least two swollen joints for less than 6 months who appeared to have no other type of arthritis causing their symptoms. The 2010 criteria identified 68% as having RA, while the 1987 criteria identified 59% of these early-stage patients with RA. The researchers had 6-year follow-up data for these patients, which allowed them to compare the results of baseline assessment with each of the two criteria against the eventual, long-term clinical diagnosis of RA.

Dr. Nicolau and her associates also evaluated the 1987 and 2010 criteria using a different end point as the standard for determining which patients eventually developed RA, the number of patients with at least three erosive joints after 2 years of follow-up. Against this standard, the 2010 criteria performed virtually identically as the 1987 criteria. Both criteria identified early-stage RA with 95% sensitivity, and both accounted for 82% of early-stage patients who eventually developed RA 2 years later.

Dr. Nicolau and Dr. Silman said that they had no disclosures. Dr. Silman was a member of the committee that wrote the 2010 rheumatoid arthritis classification criteria.

BERLIN – The 2010 criteria for classifying rheumatoid arthritis accomplish what they were designed to do in patients with early disease: boost the sensitivity for identifying patients who are likely to eventually develop rheumatoid arthritis and could therefore benefit from early treatment.

A comparison of the 2010 criteria (Arthritis Rheum. 2010;62:2569-81) against the 1987 rheumatoid arthritis (RA) classification criteria (Arthritis Rheum.1987;31:315-24) in a cohort of 269 patients with early disease showed that the 2010 method increased the sensitivity for finding patients with early-stage disease who were destined eventually to develop full-blown RA over the next 6 years to 86% sensitivity, compared with 78% sensitivity for the 1987 criteria, a statistically significant difference, Dr. Julia Nicolau said at the annual meeting of the European Congress of Rheumatology.

Among the 229 patients from this group with no joint erosions detectable at baseline, the 2010 criteria worked even better, primarily because the specificity of the criteria jumped from 59% in the full cohort examined to 71% when patients with one or more joint erosions were excluded. The positive predictive value of the 2010 criteria was 80% for the entire group of 269 (compared with 81% for the 1987 criteria), but in the subgroup without erosions, the positive predictive value of the 2010 criteria was 85%, said Dr. Nicolau, a rheumatologist at Rouen (France) University Hospital.

In addition, in an analysis of the area under the receiver-operator curve the 2010 criteria applied to patients without any erosions at baseline accounted for 82% of the confirmed RA cases after 6 years, significantly more than the 79% of cases identified by the 1987 criteria.

"The mind-set we had when we set up the [2010] criteria was to try to catch everybody [who would soon develop RA], and accept that we might treat some people who we don’t know will develop erosive disease," said Dr. Alan J. Silman, medical director of the U.K. Arthritis Research Campaign and a member of the committee that wrote the 2010 RA classification criteria. "Missing a case of RA is problematic because the interventions we have are fairly effective. Among patients with early arthritis, some will progress to persistent, erosive disease, and the issue is what should we use to identify the patients who should receive intervention" at an early stage. "We may treat some patients who won’t have bad outcomes [and won’t progress to erosive joints], but we accept that we need to treat a lot of patients to prevent the bad outcomes."

The results reported by Dr. Nicolau used the Very Early Arthritis Cohort, which included 269 patients with at least two swollen joints for less than 6 months who appeared to have no other type of arthritis causing their symptoms. The 2010 criteria identified 68% as having RA, while the 1987 criteria identified 59% of these early-stage patients with RA. The researchers had 6-year follow-up data for these patients, which allowed them to compare the results of baseline assessment with each of the two criteria against the eventual, long-term clinical diagnosis of RA.

Dr. Nicolau and her associates also evaluated the 1987 and 2010 criteria using a different end point as the standard for determining which patients eventually developed RA, the number of patients with at least three erosive joints after 2 years of follow-up. Against this standard, the 2010 criteria performed virtually identically as the 1987 criteria. Both criteria identified early-stage RA with 95% sensitivity, and both accounted for 82% of early-stage patients who eventually developed RA 2 years later.

Dr. Nicolau and Dr. Silman said that they had no disclosures. Dr. Silman was a member of the committee that wrote the 2010 rheumatoid arthritis classification criteria.

BERLIN – Tocilizumab monotherapy worked substantially better than adalimumab monotherapy in a head-to-head randomized trial of 326 rheumatoid arthritis patients, suggesting that the newer drug tocilizumab has superior efficacy compared with drugs that block tumor necrosis factor, at least when methotrexate isn’t coadministered.

After 24 weeks of treatment, tocilizumab monotherapy produced remission of rheumatoid arthritis (RA) in 40% of patients, based on their disease activity score in 28 joints (DAS28), compared with an 11% remission rate in patients on adalimumab monotherapy, a significant difference, Dr. Cem Gabay reported at the annual European Congress of Rheumatology.

This is the first direct RA comparison of representatives of these two drug classes, both of which block cytokines, said Dr. Gabay, professor of pathology and immunology at the University of Geneva. Both tocilizumab (Actemra) and adalimumab (Humira) have Food and Drug Administration labeling for the treatment of RA.

"Anti-TNF [tumor necrosis factor] drugs remain the first biologic drugs to try, based on EULAR recommendations, but we showed that if a patient is on monotherapy, tocilizumab might be the better choice," Dr. Gabay said in an interview.

"If a patient is on methotrexate and tolerates methotrexate, there is no reason to stop," and those patients should continue to get a TNF inhibitor. "But many patients don’t tolerate methotrexate, and in these patients tocilizumab may be the choice for a biologic as monotherapy." About a third of RA patients who receive a biologic drug get it as monotherapy and are not on concomitant therapy with a synthetic, disease-modifying antirheumatic drug (DMARD) such as methotrexate, usually because they don’t tolerate those drugs or because their preference is to avoid them.

"This needs to be confirmed by other studies, but according to these new data, when patients cannot tolerate a synthetic DMARD they will do better on tocilizumab than with an anti-TNF drug," Dr. Gabay said. "But for the majority of patients [who are on synthetic DMARD treatment], an anti-TNF drug remains the first line. They have been around for 10 years, and are much more studied than tocilizumab."

The finding is important for RA practice because "we don’t have many head-to-head studies of biologics," commented Dr. Xavier Mariette, professor and head of rheumatology at Bicetre Hospital in Paris. But he questioned the fairness of using adalimumab as the study’s representative anti-TNF drug, noting its documented immunogenicity, especially when used in monotherapy. "Other monotherapy would have been more appropriate," he said.

In response, Dr. Gabay highlighted the separation in average DAS28 scores that occurred after 8 weeks of treatment between the two study arms, the point when patients on tocilizumab began to have significantly lower scores than the adalimumab patients. The difference seems to occur too soon to result from an immune reaction to adalimumab, Dr. Gabay said.

The ADACTA trial enrolled 326 adults with RA at 82 centers in 15 countries including the United States. Enrollment criteria included having RA for at least 6 months and a DAS28 score of more than 5.1. All patients were naive for biologic drugs, but they could have had prior or current treatment with methotrexate or other synthetic DMARDs. All DMARDs were withdrawn at least 2 weeks before the study began. The patients had a mean age of 53 years, 80% were women, their average RA duration was more than 6 years, they had a history with average of two DMARDs, slightly more than half were on an oral steroid, and their mean DAS28 score was about 6.7.

The researchers randomized patients to receive 8 mg/kg tocilizumab intravenously every 4 weeks, or 40 mg of subcutaneous adalimumab every 2 weeks. Patients also received placebo treatments to blind everyone to the active-drug assignments.

For the study’s primary end point, average change in DAS28 score from baseline to 24 weeks on treatment, the reductions averaged 1.8 points in the adalimumab group and 3.3 points in the tocilizumab group, a significant difference. Low disease activity, defined as a DAS28 score of 3.2 or less, occurred in 20% of the adalimumab patients and in 52% of those on tocilizumab, also a significant difference. A 20% improvement by the criteria of the American College of Rheumatology (ACR20) occurred in 49% of the adalimumab patients, and their ACR50 and ACR70 rates were 28% and 18%, respectively. In the tocilizumab patients, the ACR20/50/70 rates were 65%, 47%, and 33%, respectively.

The rates of serious adverse events, infections, and serious infections were all similar in the two treatment arms. Infections occurred in 42% of the adalimumab patients and in 48% of those on tocilizumab, and serious infections occurred in 3% of both groups. Serious adverse events occurred in 10% of the adalimumab patients and in 12% of those on tocilizumab. Patients on tocilizumab had moderately higher rates of elevated liver enzymes. The tocilizumab patients had a 31% rate of enzymes elevated from above the upper limit of normal (ULN) to 2.5-fold the ULN, compared with 25% of the adalimumab patients; and liver enzyme elevations of 2.6-5.0 times the ULN occurred in 6% of the tocilizumab patients and in 2% of those on adalimumab. Tocilizumab showed "no new or unexpected adverse effects," Dr. Gabay said.

The study was sponsored by Roche, the company that markets tocilizumab. Dr. Gabay reported receiving research support from and being a consultant to Roche and several other drug companies. Dr. Mariette reported receiving research support from Roche and several other drug companies.

BERLIN – Tocilizumab monotherapy worked substantially better than adalimumab monotherapy in a head-to-head randomized trial of 326 rheumatoid arthritis patients, suggesting that the newer drug tocilizumab has superior efficacy compared with drugs that block tumor necrosis factor, at least when methotrexate isn’t coadministered.

After 24 weeks of treatment, tocilizumab monotherapy produced remission of rheumatoid arthritis (RA) in 40% of patients, based on their disease activity score in 28 joints (DAS28), compared with an 11% remission rate in patients on adalimumab monotherapy, a significant difference, Dr. Cem Gabay reported at the annual European Congress of Rheumatology.

This is the first direct RA comparison of representatives of these two drug classes, both of which block cytokines, said Dr. Gabay, professor of pathology and immunology at the University of Geneva. Both tocilizumab (Actemra) and adalimumab (Humira) have Food and Drug Administration labeling for the treatment of RA.

"Anti-TNF [tumor necrosis factor] drugs remain the first biologic drugs to try, based on EULAR recommendations, but we showed that if a patient is on monotherapy, tocilizumab might be the better choice," Dr. Gabay said in an interview.

"If a patient is on methotrexate and tolerates methotrexate, there is no reason to stop," and those patients should continue to get a TNF inhibitor. "But many patients don’t tolerate methotrexate, and in these patients tocilizumab may be the choice for a biologic as monotherapy." About a third of RA patients who receive a biologic drug get it as monotherapy and are not on concomitant therapy with a synthetic, disease-modifying antirheumatic drug (DMARD) such as methotrexate, usually because they don’t tolerate those drugs or because their preference is to avoid them.

"This needs to be confirmed by other studies, but according to these new data, when patients cannot tolerate a synthetic DMARD they will do better on tocilizumab than with an anti-TNF drug," Dr. Gabay said. "But for the majority of patients [who are on synthetic DMARD treatment], an anti-TNF drug remains the first line. They have been around for 10 years, and are much more studied than tocilizumab."

The finding is important for RA practice because "we don’t have many head-to-head studies of biologics," commented Dr. Xavier Mariette, professor and head of rheumatology at Bicetre Hospital in Paris. But he questioned the fairness of using adalimumab as the study’s representative anti-TNF drug, noting its documented immunogenicity, especially when used in monotherapy. "Other monotherapy would have been more appropriate," he said.

In response, Dr. Gabay highlighted the separation in average DAS28 scores that occurred after 8 weeks of treatment between the two study arms, the point when patients on tocilizumab began to have significantly lower scores than the adalimumab patients. The difference seems to occur too soon to result from an immune reaction to adalimumab, Dr. Gabay said.

The ADACTA trial enrolled 326 adults with RA at 82 centers in 15 countries including the United States. Enrollment criteria included having RA for at least 6 months and a DAS28 score of more than 5.1. All patients were naive for biologic drugs, but they could have had prior or current treatment with methotrexate or other synthetic DMARDs. All DMARDs were withdrawn at least 2 weeks before the study began. The patients had a mean age of 53 years, 80% were women, their average RA duration was more than 6 years, they had a history with average of two DMARDs, slightly more than half were on an oral steroid, and their mean DAS28 score was about 6.7.

The researchers randomized patients to receive 8 mg/kg tocilizumab intravenously every 4 weeks, or 40 mg of subcutaneous adalimumab every 2 weeks. Patients also received placebo treatments to blind everyone to the active-drug assignments.

For the study’s primary end point, average change in DAS28 score from baseline to 24 weeks on treatment, the reductions averaged 1.8 points in the adalimumab group and 3.3 points in the tocilizumab group, a significant difference. Low disease activity, defined as a DAS28 score of 3.2 or less, occurred in 20% of the adalimumab patients and in 52% of those on tocilizumab, also a significant difference. A 20% improvement by the criteria of the American College of Rheumatology (ACR20) occurred in 49% of the adalimumab patients, and their ACR50 and ACR70 rates were 28% and 18%, respectively. In the tocilizumab patients, the ACR20/50/70 rates were 65%, 47%, and 33%, respectively.

The rates of serious adverse events, infections, and serious infections were all similar in the two treatment arms. Infections occurred in 42% of the adalimumab patients and in 48% of those on tocilizumab, and serious infections occurred in 3% of both groups. Serious adverse events occurred in 10% of the adalimumab patients and in 12% of those on tocilizumab. Patients on tocilizumab had moderately higher rates of elevated liver enzymes. The tocilizumab patients had a 31% rate of enzymes elevated from above the upper limit of normal (ULN) to 2.5-fold the ULN, compared with 25% of the adalimumab patients; and liver enzyme elevations of 2.6-5.0 times the ULN occurred in 6% of the tocilizumab patients and in 2% of those on adalimumab. Tocilizumab showed "no new or unexpected adverse effects," Dr. Gabay said.

The study was sponsored by Roche, the company that markets tocilizumab. Dr. Gabay reported receiving research support from and being a consultant to Roche and several other drug companies. Dr. Mariette reported receiving research support from Roche and several other drug companies.

BERLIN – Tocilizumab monotherapy worked substantially better than adalimumab monotherapy in a head-to-head randomized trial of 326 rheumatoid arthritis patients, suggesting that the newer drug tocilizumab has superior efficacy compared with drugs that block tumor necrosis factor, at least when methotrexate isn’t coadministered.

After 24 weeks of treatment, tocilizumab monotherapy produced remission of rheumatoid arthritis (RA) in 40% of patients, based on their disease activity score in 28 joints (DAS28), compared with an 11% remission rate in patients on adalimumab monotherapy, a significant difference, Dr. Cem Gabay reported at the annual European Congress of Rheumatology.

This is the first direct RA comparison of representatives of these two drug classes, both of which block cytokines, said Dr. Gabay, professor of pathology and immunology at the University of Geneva. Both tocilizumab (Actemra) and adalimumab (Humira) have Food and Drug Administration labeling for the treatment of RA.

"Anti-TNF [tumor necrosis factor] drugs remain the first biologic drugs to try, based on EULAR recommendations, but we showed that if a patient is on monotherapy, tocilizumab might be the better choice," Dr. Gabay said in an interview.

"If a patient is on methotrexate and tolerates methotrexate, there is no reason to stop," and those patients should continue to get a TNF inhibitor. "But many patients don’t tolerate methotrexate, and in these patients tocilizumab may be the choice for a biologic as monotherapy." About a third of RA patients who receive a biologic drug get it as monotherapy and are not on concomitant therapy with a synthetic, disease-modifying antirheumatic drug (DMARD) such as methotrexate, usually because they don’t tolerate those drugs or because their preference is to avoid them.

"This needs to be confirmed by other studies, but according to these new data, when patients cannot tolerate a synthetic DMARD they will do better on tocilizumab than with an anti-TNF drug," Dr. Gabay said. "But for the majority of patients [who are on synthetic DMARD treatment], an anti-TNF drug remains the first line. They have been around for 10 years, and are much more studied than tocilizumab."

The finding is important for RA practice because "we don’t have many head-to-head studies of biologics," commented Dr. Xavier Mariette, professor and head of rheumatology at Bicetre Hospital in Paris. But he questioned the fairness of using adalimumab as the study’s representative anti-TNF drug, noting its documented immunogenicity, especially when used in monotherapy. "Other monotherapy would have been more appropriate," he said.

In response, Dr. Gabay highlighted the separation in average DAS28 scores that occurred after 8 weeks of treatment between the two study arms, the point when patients on tocilizumab began to have significantly lower scores than the adalimumab patients. The difference seems to occur too soon to result from an immune reaction to adalimumab, Dr. Gabay said.

The ADACTA trial enrolled 326 adults with RA at 82 centers in 15 countries including the United States. Enrollment criteria included having RA for at least 6 months and a DAS28 score of more than 5.1. All patients were naive for biologic drugs, but they could have had prior or current treatment with methotrexate or other synthetic DMARDs. All DMARDs were withdrawn at least 2 weeks before the study began. The patients had a mean age of 53 years, 80% were women, their average RA duration was more than 6 years, they had a history with average of two DMARDs, slightly more than half were on an oral steroid, and their mean DAS28 score was about 6.7.

The researchers randomized patients to receive 8 mg/kg tocilizumab intravenously every 4 weeks, or 40 mg of subcutaneous adalimumab every 2 weeks. Patients also received placebo treatments to blind everyone to the active-drug assignments.

For the study’s primary end point, average change in DAS28 score from baseline to 24 weeks on treatment, the reductions averaged 1.8 points in the adalimumab group and 3.3 points in the tocilizumab group, a significant difference. Low disease activity, defined as a DAS28 score of 3.2 or less, occurred in 20% of the adalimumab patients and in 52% of those on tocilizumab, also a significant difference. A 20% improvement by the criteria of the American College of Rheumatology (ACR20) occurred in 49% of the adalimumab patients, and their ACR50 and ACR70 rates were 28% and 18%, respectively. In the tocilizumab patients, the ACR20/50/70 rates were 65%, 47%, and 33%, respectively.

The rates of serious adverse events, infections, and serious infections were all similar in the two treatment arms. Infections occurred in 42% of the adalimumab patients and in 48% of those on tocilizumab, and serious infections occurred in 3% of both groups. Serious adverse events occurred in 10% of the adalimumab patients and in 12% of those on tocilizumab. Patients on tocilizumab had moderately higher rates of elevated liver enzymes. The tocilizumab patients had a 31% rate of enzymes elevated from above the upper limit of normal (ULN) to 2.5-fold the ULN, compared with 25% of the adalimumab patients; and liver enzyme elevations of 2.6-5.0 times the ULN occurred in 6% of the tocilizumab patients and in 2% of those on adalimumab. Tocilizumab showed "no new or unexpected adverse effects," Dr. Gabay said.

The study was sponsored by Roche, the company that markets tocilizumab. Dr. Gabay reported receiving research support from and being a consultant to Roche and several other drug companies. Dr. Mariette reported receiving research support from Roche and several other drug companies.

BERLIN – The combination of an elevated level of interferon gene expression and a low level of circulating B cells identified patients with arthralgia who had a high rate of progression to rheumatoid arthritis in a validation study of 115 patients at one center.

After 2 years of follow-up, about 70% of patients with a high level of interferon gene expression and a low level of B cells in their peripheral blood had developed rheumatoid arthritis (RA), while in contrast about 20% of arthralgia patients with low interferon gene expression and a high B-cell level developed RA, Joyce Lubbers said at the annual European Congress of Rheumatology.

Some of Ms. Lubbers’ associates on the study had previously shown, in a different group of 109 patients with arthralgia, that high interferon gene expression was linked to an increased rate of progression to RA, and that high expression of genes involved in B-cell activation was linked to a reduced risk for progressing to RA (Arthritis Rheum. 2010;62:694-704). Hence, the new findings that Ms. Lubbers reported validated the results of the previous study.

"We’ve now shown this in two independent cohorts, and we’re looking at a third group," said Ms. Lubbers, a researcher working on inflammatory disease profiling at VU University Medical Center in Amsterdam.

In practice, these easily obtained lab markers – interferon gene expression and B cell count – can couple with a patient’s clinical profile to estimate the risk of developing RA.

The next step is to test whether an intervention in arthralgia patients at high risk for progression to RA can delay or prevent the progression, or make RA less severe once it develops. Researchers in Amsterdam are currently testing whether treatment of high-risk arthralgia patients with rituximab can have a positive effect on RA progression, she said in an interview.

The study included 115 patients with arthralgia who did not have RA, joint erosions, or a history of treatment with any disease-modifying antirheumatic drug at one center in Amsterdam. During a median 23 months of follow-up, 44 patients (38%) developed RA, after a median of 8 months.

At baseline, the researchers calculated an interferon gene score for each patient, based on their expression of seven different genes involved in responses to interferon. Patients who progressed to RA had an average interferon score at baseline that was about twice the average in the nonprogressors. At 2 years of follow-up, about 60% of the high gene expressors had progressed to RA, compared with about 30% of the low expressors, a statistically significant difference.

Adding data on the number of peripheral blood B cells, quantified by fluorescent-activated cell sorting, produced a statistically significant refinement of the progression rate.

It makes physiologic sense that interferon responses and blood levels of B cells would correlate with progression to early-stage RA, Ms. Lubbers said. A low level of B cells in blood suggests that a higher than normal number of B cells had migrated out of the blood and into tissue, such as into the synovium, Ms. Lubbers said.

Ms. Lubbers said that she had no disclosures. The VU Medical Center has a patent pending on using the markers studied for identifying preclinical RA.

BERLIN – The combination of an elevated level of interferon gene expression and a low level of circulating B cells identified patients with arthralgia who had a high rate of progression to rheumatoid arthritis in a validation study of 115 patients at one center.

After 2 years of follow-up, about 70% of patients with a high level of interferon gene expression and a low level of B cells in their peripheral blood had developed rheumatoid arthritis (RA), while in contrast about 20% of arthralgia patients with low interferon gene expression and a high B-cell level developed RA, Joyce Lubbers said at the annual European Congress of Rheumatology.

Some of Ms. Lubbers’ associates on the study had previously shown, in a different group of 109 patients with arthralgia, that high interferon gene expression was linked to an increased rate of progression to RA, and that high expression of genes involved in B-cell activation was linked to a reduced risk for progressing to RA (Arthritis Rheum. 2010;62:694-704). Hence, the new findings that Ms. Lubbers reported validated the results of the previous study.

"We’ve now shown this in two independent cohorts, and we’re looking at a third group," said Ms. Lubbers, a researcher working on inflammatory disease profiling at VU University Medical Center in Amsterdam.

In practice, these easily obtained lab markers – interferon gene expression and B cell count – can couple with a patient’s clinical profile to estimate the risk of developing RA.

The next step is to test whether an intervention in arthralgia patients at high risk for progression to RA can delay or prevent the progression, or make RA less severe once it develops. Researchers in Amsterdam are currently testing whether treatment of high-risk arthralgia patients with rituximab can have a positive effect on RA progression, she said in an interview.

The study included 115 patients with arthralgia who did not have RA, joint erosions, or a history of treatment with any disease-modifying antirheumatic drug at one center in Amsterdam. During a median 23 months of follow-up, 44 patients (38%) developed RA, after a median of 8 months.

At baseline, the researchers calculated an interferon gene score for each patient, based on their expression of seven different genes involved in responses to interferon. Patients who progressed to RA had an average interferon score at baseline that was about twice the average in the nonprogressors. At 2 years of follow-up, about 60% of the high gene expressors had progressed to RA, compared with about 30% of the low expressors, a statistically significant difference.

Adding data on the number of peripheral blood B cells, quantified by fluorescent-activated cell sorting, produced a statistically significant refinement of the progression rate.

It makes physiologic sense that interferon responses and blood levels of B cells would correlate with progression to early-stage RA, Ms. Lubbers said. A low level of B cells in blood suggests that a higher than normal number of B cells had migrated out of the blood and into tissue, such as into the synovium, Ms. Lubbers said.

Ms. Lubbers said that she had no disclosures. The VU Medical Center has a patent pending on using the markers studied for identifying preclinical RA.

BERLIN – The combination of an elevated level of interferon gene expression and a low level of circulating B cells identified patients with arthralgia who had a high rate of progression to rheumatoid arthritis in a validation study of 115 patients at one center.

After 2 years of follow-up, about 70% of patients with a high level of interferon gene expression and a low level of B cells in their peripheral blood had developed rheumatoid arthritis (RA), while in contrast about 20% of arthralgia patients with low interferon gene expression and a high B-cell level developed RA, Joyce Lubbers said at the annual European Congress of Rheumatology.

Some of Ms. Lubbers’ associates on the study had previously shown, in a different group of 109 patients with arthralgia, that high interferon gene expression was linked to an increased rate of progression to RA, and that high expression of genes involved in B-cell activation was linked to a reduced risk for progressing to RA (Arthritis Rheum. 2010;62:694-704). Hence, the new findings that Ms. Lubbers reported validated the results of the previous study.

"We’ve now shown this in two independent cohorts, and we’re looking at a third group," said Ms. Lubbers, a researcher working on inflammatory disease profiling at VU University Medical Center in Amsterdam.

In practice, these easily obtained lab markers – interferon gene expression and B cell count – can couple with a patient’s clinical profile to estimate the risk of developing RA.

The next step is to test whether an intervention in arthralgia patients at high risk for progression to RA can delay or prevent the progression, or make RA less severe once it develops. Researchers in Amsterdam are currently testing whether treatment of high-risk arthralgia patients with rituximab can have a positive effect on RA progression, she said in an interview.

The study included 115 patients with arthralgia who did not have RA, joint erosions, or a history of treatment with any disease-modifying antirheumatic drug at one center in Amsterdam. During a median 23 months of follow-up, 44 patients (38%) developed RA, after a median of 8 months.

At baseline, the researchers calculated an interferon gene score for each patient, based on their expression of seven different genes involved in responses to interferon. Patients who progressed to RA had an average interferon score at baseline that was about twice the average in the nonprogressors. At 2 years of follow-up, about 60% of the high gene expressors had progressed to RA, compared with about 30% of the low expressors, a statistically significant difference.

Adding data on the number of peripheral blood B cells, quantified by fluorescent-activated cell sorting, produced a statistically significant refinement of the progression rate.

It makes physiologic sense that interferon responses and blood levels of B cells would correlate with progression to early-stage RA, Ms. Lubbers said. A low level of B cells in blood suggests that a higher than normal number of B cells had migrated out of the blood and into tissue, such as into the synovium, Ms. Lubbers said.

Ms. Lubbers said that she had no disclosures. The VU Medical Center has a patent pending on using the markers studied for identifying preclinical RA.

BERLIN – Treated patients in remission from rheumatoid arthritis who are rheumatoid factor–positive and have a high level of joint synovitis visible on MRI have an increased risk for progressive joint damage, according to a review of 287 patients from six international registry cohorts.

The presence of joint synovitis during remission signaled an especially poor prognosis in rheumatoid factor (RF)-positive patients, who accounted for slightly more than half of the group studied. Among rheumatoid arthritis (RA) patients in remission who were RF-positive and had an RA MRI score (RAMRIS) of 6 or more, 42% subsequently had progressive joint erosions, Dr. Espen A. Haavardsholm said at the annual European Congress of Rheumatology.

In contrast, among RF-positive patients in remission with a RAMRIS of 5 or less, 12% had radiographic progression. Among all RF-negative patients, the rate of radiographic progression was less than 20% regardless of their RAMRIS.

What this means is that when RA patients are in remission on treatment, if they are RF-negative their risk of radiographic progression is low and MRI examinations aren’t needed. But if they are RF-positive and if they score 6 or more for synovitis on MRI, their risk for progression is high, and they need close monitoring and no change in their treatment. Patients with a score of 5 or less, as well as those who are RF-negative, are candidates for less rigorous follow-up and a possible step-down in their treatment, said Dr. Haavardsholm, a rheumatologist at Diakohnjemmet Hospital in Oslo.

"When patients are in remission, do you keep them on their current treatment or step down? We suggest you take an MRI and decide based on that," he said in an interview. Although ideally a prospective study should be done to test this approach, "I would manage patients this way right now," Dr. Haavardsholm said. "If a patient [in remission] is RF-positive, they are a good candidate for MRI; that’s the implication of our study."

Dr. Haavardsholm and his associates from the OMERACT (Outcome Measures in Rheumatology) MRI in RA Task Force used data collected on 287 RA patients in remission or with low disease activity on treatment who were in registries in Oslo; Paris; Sydney; Leeds, England; and two different cohorts in Copenhagen. The patients ranged from 43 to 63 years old, and their average RA duration was about 2 years. Virtually all patients were on treatment with a disease-modifying antirheumatic drug, 15% were also on treatment with a biologic agent, and a quarter were on an oral corticosteroid. Nearly three-quarters were in remission, with the rest having low disease activity. The researchers had baseline MRI results for all patients.

A multivariate stepwise regression analysis and calculation of a receiver-operator curve for various cutoffs of the RAMRIS for synovitis showed that best dichotomous separation occurred when a RAMRIS of 0-5 was considered low and a score of 6 or more was considered high. Using this cutoff, the researchers found that among RF-positive patients, those with a score of at least 6 had a 4.4-fold increased risk for progressive joint disease compared with patients with a baseline score of 5 or less, a statistically significant difference, Dr. Haavardsholm reported. Among patients who were RF-negative, a RAMRIS of 6 or more boosted the risk for joint progression by 9% compared with patients with a score of 5 or less, a difference that was not statistically significant.

Dr. Haavardsholm said that he had no disclosures.

BERLIN – Treated patients in remission from rheumatoid arthritis who are rheumatoid factor–positive and have a high level of joint synovitis visible on MRI have an increased risk for progressive joint damage, according to a review of 287 patients from six international registry cohorts.

The presence of joint synovitis during remission signaled an especially poor prognosis in rheumatoid factor (RF)-positive patients, who accounted for slightly more than half of the group studied. Among rheumatoid arthritis (RA) patients in remission who were RF-positive and had an RA MRI score (RAMRIS) of 6 or more, 42% subsequently had progressive joint erosions, Dr. Espen A. Haavardsholm said at the annual European Congress of Rheumatology.

In contrast, among RF-positive patients in remission with a RAMRIS of 5 or less, 12% had radiographic progression. Among all RF-negative patients, the rate of radiographic progression was less than 20% regardless of their RAMRIS.

What this means is that when RA patients are in remission on treatment, if they are RF-negative their risk of radiographic progression is low and MRI examinations aren’t needed. But if they are RF-positive and if they score 6 or more for synovitis on MRI, their risk for progression is high, and they need close monitoring and no change in their treatment. Patients with a score of 5 or less, as well as those who are RF-negative, are candidates for less rigorous follow-up and a possible step-down in their treatment, said Dr. Haavardsholm, a rheumatologist at Diakohnjemmet Hospital in Oslo.

"When patients are in remission, do you keep them on their current treatment or step down? We suggest you take an MRI and decide based on that," he said in an interview. Although ideally a prospective study should be done to test this approach, "I would manage patients this way right now," Dr. Haavardsholm said. "If a patient [in remission] is RF-positive, they are a good candidate for MRI; that’s the implication of our study."

Dr. Haavardsholm and his associates from the OMERACT (Outcome Measures in Rheumatology) MRI in RA Task Force used data collected on 287 RA patients in remission or with low disease activity on treatment who were in registries in Oslo; Paris; Sydney; Leeds, England; and two different cohorts in Copenhagen. The patients ranged from 43 to 63 years old, and their average RA duration was about 2 years. Virtually all patients were on treatment with a disease-modifying antirheumatic drug, 15% were also on treatment with a biologic agent, and a quarter were on an oral corticosteroid. Nearly three-quarters were in remission, with the rest having low disease activity. The researchers had baseline MRI results for all patients.

A multivariate stepwise regression analysis and calculation of a receiver-operator curve for various cutoffs of the RAMRIS for synovitis showed that best dichotomous separation occurred when a RAMRIS of 0-5 was considered low and a score of 6 or more was considered high. Using this cutoff, the researchers found that among RF-positive patients, those with a score of at least 6 had a 4.4-fold increased risk for progressive joint disease compared with patients with a baseline score of 5 or less, a statistically significant difference, Dr. Haavardsholm reported. Among patients who were RF-negative, a RAMRIS of 6 or more boosted the risk for joint progression by 9% compared with patients with a score of 5 or less, a difference that was not statistically significant.

Dr. Haavardsholm said that he had no disclosures.

BERLIN – Treated patients in remission from rheumatoid arthritis who are rheumatoid factor–positive and have a high level of joint synovitis visible on MRI have an increased risk for progressive joint damage, according to a review of 287 patients from six international registry cohorts.

The presence of joint synovitis during remission signaled an especially poor prognosis in rheumatoid factor (RF)-positive patients, who accounted for slightly more than half of the group studied. Among rheumatoid arthritis (RA) patients in remission who were RF-positive and had an RA MRI score (RAMRIS) of 6 or more, 42% subsequently had progressive joint erosions, Dr. Espen A. Haavardsholm said at the annual European Congress of Rheumatology.

In contrast, among RF-positive patients in remission with a RAMRIS of 5 or less, 12% had radiographic progression. Among all RF-negative patients, the rate of radiographic progression was less than 20% regardless of their RAMRIS.

What this means is that when RA patients are in remission on treatment, if they are RF-negative their risk of radiographic progression is low and MRI examinations aren’t needed. But if they are RF-positive and if they score 6 or more for synovitis on MRI, their risk for progression is high, and they need close monitoring and no change in their treatment. Patients with a score of 5 or less, as well as those who are RF-negative, are candidates for less rigorous follow-up and a possible step-down in their treatment, said Dr. Haavardsholm, a rheumatologist at Diakohnjemmet Hospital in Oslo.

"When patients are in remission, do you keep them on their current treatment or step down? We suggest you take an MRI and decide based on that," he said in an interview. Although ideally a prospective study should be done to test this approach, "I would manage patients this way right now," Dr. Haavardsholm said. "If a patient [in remission] is RF-positive, they are a good candidate for MRI; that’s the implication of our study."

Dr. Haavardsholm and his associates from the OMERACT (Outcome Measures in Rheumatology) MRI in RA Task Force used data collected on 287 RA patients in remission or with low disease activity on treatment who were in registries in Oslo; Paris; Sydney; Leeds, England; and two different cohorts in Copenhagen. The patients ranged from 43 to 63 years old, and their average RA duration was about 2 years. Virtually all patients were on treatment with a disease-modifying antirheumatic drug, 15% were also on treatment with a biologic agent, and a quarter were on an oral corticosteroid. Nearly three-quarters were in remission, with the rest having low disease activity. The researchers had baseline MRI results for all patients.

A multivariate stepwise regression analysis and calculation of a receiver-operator curve for various cutoffs of the RAMRIS for synovitis showed that best dichotomous separation occurred when a RAMRIS of 0-5 was considered low and a score of 6 or more was considered high. Using this cutoff, the researchers found that among RF-positive patients, those with a score of at least 6 had a 4.4-fold increased risk for progressive joint disease compared with patients with a baseline score of 5 or less, a statistically significant difference, Dr. Haavardsholm reported. Among patients who were RF-negative, a RAMRIS of 6 or more boosted the risk for joint progression by 9% compared with patients with a score of 5 or less, a difference that was not statistically significant.

Dr. Haavardsholm said that he had no disclosures.

BERLIN – Two new Janus kinase inhibitor drugs have shown good safety and efficacy for clinical rheumatoid arthritis, following in the footsteps of the JAK inhibitor tofacitinib, researchers reported at the annual European Congress of Rheumatology.

Baricitinib showed safety and promising efficacy in a multicenter, phase 2 study with 301 rheumatoid arthritis (RA) patients, said Dr. Edward Keystone, professor of medicine at the University of Toronto. And in results from a second study, GLPG0634 showed good safety and efficacy in a placebo-controlled, early phase 2 study with 36 RA patients. In both cases the results should propel these drugs into wider clinical testing.

Mitchel Zoler/IMNG Medical Media

The results also hinted that different JAK inhibitors may produce somewhat different clinical effects depending on exactly which Janus kinases they inhibit. Tofacitinib blocks all four JAKs, but its effect seems strongest on JAK3. Baricitinib specifically inhibits JAK1 and JAK2, while GLPG0634 specifically inhibits only JAK1, said speakers at the meeting.

"JAK selectivity makes a difference," said Dr. Frédéric Vanhoutte, lead investigator of the GLPG0634 study and a staff member at Galapagos, the Belgium drug company developing the agent.

The baricitinib study randomized patients on methotrexate to any of four drug dosages, given as a single, daily oral treatment, or placebo and looked at safety and efficacy after 12 weeks on treatment. At 12 weeks 76% of patients treated with either of the two highest baricitinib dosages (4 mg or 8 mg daily) had an American College of Rheumatology (ACR) 20 response, compared with 41% of the placebo patients, a statistically significant difference for the study’s primary end point, reported Dr. Keystone, who also directs the center for arthritis and autoimmune disease at Mount Sinai Hospital in Toronto. The incidence of remission at 12 weeks, based on a simple disease activity index (SDAI) score of 3.3 or less, occurred in 18% of patients on the 4-mg/day baricitinib plus methotrexate regimen compared with 1% of patients on methotrexate and placebo; 8% of patients who received 8 mg daily also achieved remission.

For safety, baricitinib appeared well tolerated, with an adverse event profile similar to the placebo arm. The results showed dose-dependent reductions in hemoglobin and neutrophils, and an increased level of low density lipoprotein cholesterol, but effects that surpassed the placebo arm primarily occurred in patients who received 8 mg of the drug daily. "The reductions in hemoglobin and neutrophils were of the same order of magnitude as with tofacitinib," Dr. Keystone said in an interview. "Some had thought that baricitinib might be more inhibitory to the hematologic system than tofacitinib, but it wasn’t very."

The study of 36 RA patients on methotrexate who received either of two dosages of the oral JAK 1 inhibitor GLPG0634 or placebo ran for 4 weeks at one center in Europe. The 100-mg b.i.d. dosage led to 92% of patients meeting ACR 20 criteria after 4 weeks, compared with 75% of patients who received 200 mg once daily and 33% among placebo patients, reported Dr. Vanhoutte. Treatment with the JAK1 inhibitor also led to higher remission rates and drops in C-reactive protein.

For safety, the JAK1 inhibitor actually boosted hemoglobin levels, led to no rise in LDL cholesterol or liver enzymes, and produced a "modest" reduction in neutrophils and platelets. Dr. Vanhoutte called the overall safety results "very encouraging."

The baricitinib trial was sponsored by Lilly, the company developing the drug. Dr. Keystone said that he has received research support from Lilly, and that he has received research support and has served as a consultant for several other drug companies. The GLPG0634 study was sponsored by Galapagos. Dr. Vanhoutte said that he is an employee of Galapagos.

BERLIN – Two new Janus kinase inhibitor drugs have shown good safety and efficacy for clinical rheumatoid arthritis, following in the footsteps of the JAK inhibitor tofacitinib, researchers reported at the annual European Congress of Rheumatology.

Baricitinib showed safety and promising efficacy in a multicenter, phase 2 study with 301 rheumatoid arthritis (RA) patients, said Dr. Edward Keystone, professor of medicine at the University of Toronto. And in results from a second study, GLPG0634 showed good safety and efficacy in a placebo-controlled, early phase 2 study with 36 RA patients. In both cases the results should propel these drugs into wider clinical testing.

Mitchel Zoler/IMNG Medical Media

The results also hinted that different JAK inhibitors may produce somewhat different clinical effects depending on exactly which Janus kinases they inhibit. Tofacitinib blocks all four JAKs, but its effect seems strongest on JAK3. Baricitinib specifically inhibits JAK1 and JAK2, while GLPG0634 specifically inhibits only JAK1, said speakers at the meeting.

"JAK selectivity makes a difference," said Dr. Frédéric Vanhoutte, lead investigator of the GLPG0634 study and a staff member at Galapagos, the Belgium drug company developing the agent.

The baricitinib study randomized patients on methotrexate to any of four drug dosages, given as a single, daily oral treatment, or placebo and looked at safety and efficacy after 12 weeks on treatment. At 12 weeks 76% of patients treated with either of the two highest baricitinib dosages (4 mg or 8 mg daily) had an American College of Rheumatology (ACR) 20 response, compared with 41% of the placebo patients, a statistically significant difference for the study’s primary end point, reported Dr. Keystone, who also directs the center for arthritis and autoimmune disease at Mount Sinai Hospital in Toronto. The incidence of remission at 12 weeks, based on a simple disease activity index (SDAI) score of 3.3 or less, occurred in 18% of patients on the 4-mg/day baricitinib plus methotrexate regimen compared with 1% of patients on methotrexate and placebo; 8% of patients who received 8 mg daily also achieved remission.

For safety, baricitinib appeared well tolerated, with an adverse event profile similar to the placebo arm. The results showed dose-dependent reductions in hemoglobin and neutrophils, and an increased level of low density lipoprotein cholesterol, but effects that surpassed the placebo arm primarily occurred in patients who received 8 mg of the drug daily. "The reductions in hemoglobin and neutrophils were of the same order of magnitude as with tofacitinib," Dr. Keystone said in an interview. "Some had thought that baricitinib might be more inhibitory to the hematologic system than tofacitinib, but it wasn’t very."

The study of 36 RA patients on methotrexate who received either of two dosages of the oral JAK 1 inhibitor GLPG0634 or placebo ran for 4 weeks at one center in Europe. The 100-mg b.i.d. dosage led to 92% of patients meeting ACR 20 criteria after 4 weeks, compared with 75% of patients who received 200 mg once daily and 33% among placebo patients, reported Dr. Vanhoutte. Treatment with the JAK1 inhibitor also led to higher remission rates and drops in C-reactive protein.

For safety, the JAK1 inhibitor actually boosted hemoglobin levels, led to no rise in LDL cholesterol or liver enzymes, and produced a "modest" reduction in neutrophils and platelets. Dr. Vanhoutte called the overall safety results "very encouraging."

The baricitinib trial was sponsored by Lilly, the company developing the drug. Dr. Keystone said that he has received research support from Lilly, and that he has received research support and has served as a consultant for several other drug companies. The GLPG0634 study was sponsored by Galapagos. Dr. Vanhoutte said that he is an employee of Galapagos.

BERLIN – Two new Janus kinase inhibitor drugs have shown good safety and efficacy for clinical rheumatoid arthritis, following in the footsteps of the JAK inhibitor tofacitinib, researchers reported at the annual European Congress of Rheumatology.

Baricitinib showed safety and promising efficacy in a multicenter, phase 2 study with 301 rheumatoid arthritis (RA) patients, said Dr. Edward Keystone, professor of medicine at the University of Toronto. And in results from a second study, GLPG0634 showed good safety and efficacy in a placebo-controlled, early phase 2 study with 36 RA patients. In both cases the results should propel these drugs into wider clinical testing.

Mitchel Zoler/IMNG Medical Media

The results also hinted that different JAK inhibitors may produce somewhat different clinical effects depending on exactly which Janus kinases they inhibit. Tofacitinib blocks all four JAKs, but its effect seems strongest on JAK3. Baricitinib specifically inhibits JAK1 and JAK2, while GLPG0634 specifically inhibits only JAK1, said speakers at the meeting.

"JAK selectivity makes a difference," said Dr. Frédéric Vanhoutte, lead investigator of the GLPG0634 study and a staff member at Galapagos, the Belgium drug company developing the agent.

The baricitinib study randomized patients on methotrexate to any of four drug dosages, given as a single, daily oral treatment, or placebo and looked at safety and efficacy after 12 weeks on treatment. At 12 weeks 76% of patients treated with either of the two highest baricitinib dosages (4 mg or 8 mg daily) had an American College of Rheumatology (ACR) 20 response, compared with 41% of the placebo patients, a statistically significant difference for the study’s primary end point, reported Dr. Keystone, who also directs the center for arthritis and autoimmune disease at Mount Sinai Hospital in Toronto. The incidence of remission at 12 weeks, based on a simple disease activity index (SDAI) score of 3.3 or less, occurred in 18% of patients on the 4-mg/day baricitinib plus methotrexate regimen compared with 1% of patients on methotrexate and placebo; 8% of patients who received 8 mg daily also achieved remission.

For safety, baricitinib appeared well tolerated, with an adverse event profile similar to the placebo arm. The results showed dose-dependent reductions in hemoglobin and neutrophils, and an increased level of low density lipoprotein cholesterol, but effects that surpassed the placebo arm primarily occurred in patients who received 8 mg of the drug daily. "The reductions in hemoglobin and neutrophils were of the same order of magnitude as with tofacitinib," Dr. Keystone said in an interview. "Some had thought that baricitinib might be more inhibitory to the hematologic system than tofacitinib, but it wasn’t very."

The study of 36 RA patients on methotrexate who received either of two dosages of the oral JAK 1 inhibitor GLPG0634 or placebo ran for 4 weeks at one center in Europe. The 100-mg b.i.d. dosage led to 92% of patients meeting ACR 20 criteria after 4 weeks, compared with 75% of patients who received 200 mg once daily and 33% among placebo patients, reported Dr. Vanhoutte. Treatment with the JAK1 inhibitor also led to higher remission rates and drops in C-reactive protein.

For safety, the JAK1 inhibitor actually boosted hemoglobin levels, led to no rise in LDL cholesterol or liver enzymes, and produced a "modest" reduction in neutrophils and platelets. Dr. Vanhoutte called the overall safety results "very encouraging."

The baricitinib trial was sponsored by Lilly, the company developing the drug. Dr. Keystone said that he has received research support from Lilly, and that he has received research support and has served as a consultant for several other drug companies. The GLPG0634 study was sponsored by Galapagos. Dr. Vanhoutte said that he is an employee of Galapagos.

BERLIN – Most patients with long-standing rheumatoid arthritis or other rheumatic diseases and in remission while on an anti–tumor necrosis factor drug could successfully undergo dose reduction and stay in remission, based on experience with 90 patients at one U.K. center.

In addition to maintaining a majority of patients on a reduced biologic regimen, a step that pleased patients, the program produced substantial cost savings, cutting drug costs in the unit by more than $400,000 during the course of 1 year, Dr. Jane Gibson said at the annual meeting of the European Congress of Rheumatology.

Out of 90 patients with rheumatoid arthritis (RA) or another rheumatic disease and in remission for more than a year and on a stable, standard regimen with etanercept or adalimumab, 68 (76%) successfully underwent a dosage reduction and remained in remission, said Dr. Gibson, head of the Fife Rheumatic Diseases Unit, part of the U.K. National Health Service serving the county of Fife in Scotland.

The sixteen patients who failed to stay in remission while on a reduced dosage of an anti–tumor necrosis factor (anti-TNF) drug were all successfully put back into remission with a corticosteroid injection and reinstitution of their prior treatment. Another six patients stopped their anti-TNF regimen for unrelated reasons during the period of the study, December 2010 to December 2011.

"These were patients with very long-standing disease, with some patients having RA for more than 40 years. The patients loved it; they felt it was a positive step. That was a big surprise because I thought that I’d have to persuade patients, but they thought it was great," Dr. Gibson said in an interview.

A regression analysis identified several factors significantly linked with an increased likelihood of patients’ successfully undergoing a dose reduction and remaining in remission. The strongest link was for concomitant treatment with methotrexate, according to Dr. Gibson and her associates. Patients who received methotrexate along with the anti-TNF drug had a substantially better rate of continued remission once the anti-TNF dosage dropped. Other statistically significant factors linked with successful dose reduction were concomitant treatment with any disease modifying anti-rheumatic drug (DMARD), and treatment with adalimumab (compared with treatment with etanercept). In addition, smoking history showed a strong trend toward a better rate of remission among never smokers or former smokers, but this did not reach statistical significance.

Dr. Gibson cautioned that any difference in the durability of remission on adalimumab compared with etanercept might result from the substantially shorter clinical half-lives of the two drugs. Etanercept has a half-life of 3-4 days, so cutting the dosage from the standard 50 mg subcutaneously once per week to 50 mg once every 2 weeks meant that patients scaled back to roughly four times the drug’s half-life. Thirteen of the 16 failed remissions occurred among patients switched to 50 mg etanercept every 2 weeks; among four patients scaled back to 50 mg etanercept administered every 10 days, none fell out of remission, Dr. Gibson said.

In contrast, adalimumab’s clinical half-life is about 14 days, so scaling back from the standard dosage of 40 mg subcutaneously every 2 weeks to the same amount given every 4 weeks meant that patients received the drug at intervals twice as long as the half-life. None of the 14 patients who received adalimumab every 4 weeks fell out of remission, and just two of 16 patients came out of remission when scaled back to a dosage of 40 mg adalimumab every 3 weeks.

Although concomitant methotrexate was the strongest predictor of success with scaled back dosing, only about half the patients in the Fife series were on methotrexate, and nearly a third were not on any concomitant DMARD, and so Dr. Gibson said she was unsure about any ironclad need to get patients on methotrexate or another DMARD before attempting to scale back the frequency of use of an anti-TNF agent. She said that she would attempt a small cut in anti-TNF dosage – to etanercept every 10 days or adalimumab every 3 weeks – even in patients not on a DMARD, especially if they were not current smokers, she said, although she would also frequently review these patients to watch for signs of a flare.

The premise of the approach is: "Why keep patients at the same dose? Why not see if we can adjust it?" she said.

The 84 rheumatic-disease patients who underwent an anti-TNF dose-adjustment included three-quarters with RA, with most other patients having psoriatic arthritis or ankylosing spondylitis. The average age was 57 years. Mean disease duration was more than 15 years. Their average time in continued remission at a reduced anti-TNF dosage was 11 months, with one patient followed for almost 3 years. Patients who fell out of remission tended to do so quickly, after an average of less than 4 months, and with only one patient taking longer than 5 months to fail.

Dr. Gibson said that she had no disclosures.

BERLIN – Most patients with long-standing rheumatoid arthritis or other rheumatic diseases and in remission while on an anti–tumor necrosis factor drug could successfully undergo dose reduction and stay in remission, based on experience with 90 patients at one U.K. center.

In addition to maintaining a majority of patients on a reduced biologic regimen, a step that pleased patients, the program produced substantial cost savings, cutting drug costs in the unit by more than $400,000 during the course of 1 year, Dr. Jane Gibson said at the annual meeting of the European Congress of Rheumatology.

Out of 90 patients with rheumatoid arthritis (RA) or another rheumatic disease and in remission for more than a year and on a stable, standard regimen with etanercept or adalimumab, 68 (76%) successfully underwent a dosage reduction and remained in remission, said Dr. Gibson, head of the Fife Rheumatic Diseases Unit, part of the U.K. National Health Service serving the county of Fife in Scotland.

The sixteen patients who failed to stay in remission while on a reduced dosage of an anti–tumor necrosis factor (anti-TNF) drug were all successfully put back into remission with a corticosteroid injection and reinstitution of their prior treatment. Another six patients stopped their anti-TNF regimen for unrelated reasons during the period of the study, December 2010 to December 2011.

"These were patients with very long-standing disease, with some patients having RA for more than 40 years. The patients loved it; they felt it was a positive step. That was a big surprise because I thought that I’d have to persuade patients, but they thought it was great," Dr. Gibson said in an interview.

A regression analysis identified several factors significantly linked with an increased likelihood of patients’ successfully undergoing a dose reduction and remaining in remission. The strongest link was for concomitant treatment with methotrexate, according to Dr. Gibson and her associates. Patients who received methotrexate along with the anti-TNF drug had a substantially better rate of continued remission once the anti-TNF dosage dropped. Other statistically significant factors linked with successful dose reduction were concomitant treatment with any disease modifying anti-rheumatic drug (DMARD), and treatment with adalimumab (compared with treatment with etanercept). In addition, smoking history showed a strong trend toward a better rate of remission among never smokers or former smokers, but this did not reach statistical significance.

Dr. Gibson cautioned that any difference in the durability of remission on adalimumab compared with etanercept might result from the substantially shorter clinical half-lives of the two drugs. Etanercept has a half-life of 3-4 days, so cutting the dosage from the standard 50 mg subcutaneously once per week to 50 mg once every 2 weeks meant that patients scaled back to roughly four times the drug’s half-life. Thirteen of the 16 failed remissions occurred among patients switched to 50 mg etanercept every 2 weeks; among four patients scaled back to 50 mg etanercept administered every 10 days, none fell out of remission, Dr. Gibson said.

In contrast, adalimumab’s clinical half-life is about 14 days, so scaling back from the standard dosage of 40 mg subcutaneously every 2 weeks to the same amount given every 4 weeks meant that patients received the drug at intervals twice as long as the half-life. None of the 14 patients who received adalimumab every 4 weeks fell out of remission, and just two of 16 patients came out of remission when scaled back to a dosage of 40 mg adalimumab every 3 weeks.

Although concomitant methotrexate was the strongest predictor of success with scaled back dosing, only about half the patients in the Fife series were on methotrexate, and nearly a third were not on any concomitant DMARD, and so Dr. Gibson said she was unsure about any ironclad need to get patients on methotrexate or another DMARD before attempting to scale back the frequency of use of an anti-TNF agent. She said that she would attempt a small cut in anti-TNF dosage – to etanercept every 10 days or adalimumab every 3 weeks – even in patients not on a DMARD, especially if they were not current smokers, she said, although she would also frequently review these patients to watch for signs of a flare.

The premise of the approach is: "Why keep patients at the same dose? Why not see if we can adjust it?" she said.

The 84 rheumatic-disease patients who underwent an anti-TNF dose-adjustment included three-quarters with RA, with most other patients having psoriatic arthritis or ankylosing spondylitis. The average age was 57 years. Mean disease duration was more than 15 years. Their average time in continued remission at a reduced anti-TNF dosage was 11 months, with one patient followed for almost 3 years. Patients who fell out of remission tended to do so quickly, after an average of less than 4 months, and with only one patient taking longer than 5 months to fail.

Dr. Gibson said that she had no disclosures.

BERLIN – Most patients with long-standing rheumatoid arthritis or other rheumatic diseases and in remission while on an anti–tumor necrosis factor drug could successfully undergo dose reduction and stay in remission, based on experience with 90 patients at one U.K. center.

In addition to maintaining a majority of patients on a reduced biologic regimen, a step that pleased patients, the program produced substantial cost savings, cutting drug costs in the unit by more than $400,000 during the course of 1 year, Dr. Jane Gibson said at the annual meeting of the European Congress of Rheumatology.

Out of 90 patients with rheumatoid arthritis (RA) or another rheumatic disease and in remission for more than a year and on a stable, standard regimen with etanercept or adalimumab, 68 (76%) successfully underwent a dosage reduction and remained in remission, said Dr. Gibson, head of the Fife Rheumatic Diseases Unit, part of the U.K. National Health Service serving the county of Fife in Scotland.

The sixteen patients who failed to stay in remission while on a reduced dosage of an anti–tumor necrosis factor (anti-TNF) drug were all successfully put back into remission with a corticosteroid injection and reinstitution of their prior treatment. Another six patients stopped their anti-TNF regimen for unrelated reasons during the period of the study, December 2010 to December 2011.

"These were patients with very long-standing disease, with some patients having RA for more than 40 years. The patients loved it; they felt it was a positive step. That was a big surprise because I thought that I’d have to persuade patients, but they thought it was great," Dr. Gibson said in an interview.

A regression analysis identified several factors significantly linked with an increased likelihood of patients’ successfully undergoing a dose reduction and remaining in remission. The strongest link was for concomitant treatment with methotrexate, according to Dr. Gibson and her associates. Patients who received methotrexate along with the anti-TNF drug had a substantially better rate of continued remission once the anti-TNF dosage dropped. Other statistically significant factors linked with successful dose reduction were concomitant treatment with any disease modifying anti-rheumatic drug (DMARD), and treatment with adalimumab (compared with treatment with etanercept). In addition, smoking history showed a strong trend toward a better rate of remission among never smokers or former smokers, but this did not reach statistical significance.

Dr. Gibson cautioned that any difference in the durability of remission on adalimumab compared with etanercept might result from the substantially shorter clinical half-lives of the two drugs. Etanercept has a half-life of 3-4 days, so cutting the dosage from the standard 50 mg subcutaneously once per week to 50 mg once every 2 weeks meant that patients scaled back to roughly four times the drug’s half-life. Thirteen of the 16 failed remissions occurred among patients switched to 50 mg etanercept every 2 weeks; among four patients scaled back to 50 mg etanercept administered every 10 days, none fell out of remission, Dr. Gibson said.

In contrast, adalimumab’s clinical half-life is about 14 days, so scaling back from the standard dosage of 40 mg subcutaneously every 2 weeks to the same amount given every 4 weeks meant that patients received the drug at intervals twice as long as the half-life. None of the 14 patients who received adalimumab every 4 weeks fell out of remission, and just two of 16 patients came out of remission when scaled back to a dosage of 40 mg adalimumab every 3 weeks.

Although concomitant methotrexate was the strongest predictor of success with scaled back dosing, only about half the patients in the Fife series were on methotrexate, and nearly a third were not on any concomitant DMARD, and so Dr. Gibson said she was unsure about any ironclad need to get patients on methotrexate or another DMARD before attempting to scale back the frequency of use of an anti-TNF agent. She said that she would attempt a small cut in anti-TNF dosage – to etanercept every 10 days or adalimumab every 3 weeks – even in patients not on a DMARD, especially if they were not current smokers, she said, although she would also frequently review these patients to watch for signs of a flare.

The premise of the approach is: "Why keep patients at the same dose? Why not see if we can adjust it?" she said.

The 84 rheumatic-disease patients who underwent an anti-TNF dose-adjustment included three-quarters with RA, with most other patients having psoriatic arthritis or ankylosing spondylitis. The average age was 57 years. Mean disease duration was more than 15 years. Their average time in continued remission at a reduced anti-TNF dosage was 11 months, with one patient followed for almost 3 years. Patients who fell out of remission tended to do so quickly, after an average of less than 4 months, and with only one patient taking longer than 5 months to fail.

Dr. Gibson said that she had no disclosures.

UPDATED: 06/21/2012

BERLIN – If the Food and Drug Administration follows the advice of its Arthritis Advisory Committee and approves tofacitinib as a new drug for treating rheumatoid arthritis later this summer, the oral, small-molecule drug may start to muscle in on the treatment turf now occupied by antitumor necrosis factor drugs, some experts predicted at the Annual European Congress of Rheumatology.

The attraction would be the good efficacy tofacitinib has shown in five phase III trials, a decent safety profile that looks on par with antitumor necrosis factor (TNF) drugs, and delivery as a twice-daily oral pill, a property that will give tofacitinib an edge over the anti-TNFs and other biologics that require injection or infusion.

"The fact that [tofacitinib] is oral is something of an advantage, so there will be a role for it, and it makes sense therapeutically," Dr. Joel M. Kremer said at the meeting. "But we will need to be smart" on using tofacitinib and other new drugs from the same class to treat patients with rheumatoid arthritis (RA), and their use relative to methotrexate and the biologics, said Dr. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College.

Another view was that tofacitinib will need to prove its value in larger numbers of patients, and though it will be a welcome new option – first to market from the class of Janus kinase (JAK) inhibitors – it will take its initial place post approval behind the anti-TNFs, which have more than a decade’s track record, said Dr. Iain B. McInnes in a separate talk at the meeting. Many rheumatologists "feel they will kick in after a first biologic treatment," which itself comes after first-line methotrexate, said Dr. McInnes, a rheumatologist and professor and Muirhead Chair of Medicine at the University of Glasgow, Scotland.

"The efficacy we’ve seen [from tofacitinib and other JAK inhibitors] is very encouraging, but safety will be a major driver of clinical decisions and [will] influence the order of choice. If a patient does not get an adequate response from methotrexate after 3-6 months, I would add a biologic drug, especially an anti-TNF. Inevitably, there will be less safety assurance with the new drugs. The current role for JAK inhibitors is closer to the options like abatacept, rituximab, and tocilizumab, but I think that may change" once JAK inhibitors enter routine practice, Dr. McInnes said in his talk.

"I have a lot of experience with tofacitinib, and I’m very comfortable with it; if a patient wanted this drug, I would use it," said Dr. Roy Fleischmann, who led phase II and phase III trials with tofacitinib and is codirector of rheumatology at Texas Health Presbyterian Medical Center in Dallas.

"What will practicing rheumatologists with no experience with the drug do? We’ll see what the FDA says. They might use it after methotrexate, because the data are strong. It will be up to patients: an oral drug or an injected one."

Pfizer, the company developing tofacitinib, reported data from five phase III trials and safety experience in about 4,800 patients to the FDA Advisory Committee in May. And four of the five trials examined use of the drug in RA patients as monotherapy; in combination with methotrexate; in combination with background methotrexate in patients who failed to respond to an anti-TNF drug; and in combination with a background disease modifying antirheumatic drug. The fifth study, a 2-year trial that so far has reported results from an interim, 1-year analysis only, examined tofacitinib’s ability when used in combination with methotrexate to stop radiographic progression of joint damage, compared with methotrexate alone.

Results from across the studies showed consistent efficacy, including inhibition of radiographic progression that significantly surpassed placebo patients, and a "consistent side effect profile," Dr. Kremer said. "I consider it on the same shelf for potential infections and adverse events as the [already approved] biologics," he said in an interview. He said he would shy away from prescribing tofacitinib, or any biologic, to patients who get frequent pneumonia, cellulitis, or other infections.

Perceived safety will likely be the major driver – or impediment – for use of tofacitinib during the first year or 2 after its approval, predicted Madhuri Borde, Ph.D., director of the immune and inflammatory disorders group of Decision Resources, a pharmaceutical-market consulting company in Burlington, Mass. In mid-May, Dr. Borde presented 52 U.S. rheumatologists with active RA practices the same tofacitinib data that the FDA Advisory Committee saw and she asked the rheumatologists what they thought of the drug and how they might use it soon after it hit the U.S. market.*

The results showed that rheumatologists were impressed by the efficacy results, saw safety as being similar to anti-TNF drugs, and mostly saw tofacitinib currently as a drug they would use when RA patients don’t respond to an anti-TNF agent. "For physicians, it boils down to their comfort with the safety profile," she said in an interview, and they think safety is still a little uncertain.

Although Dr. Borde conceded that "patients are wary of injections" and that oral dosing is an attractive option for many patients, physician uncertainty about safety will generally trump that. "I think safety concerns will drive caution in using tofacitinib," at least during the first couple of years on the market, until a higher comfort level is reached. It’s likely that in an effort to stimulate interest in the drug, Pfizer will price it aggressively, at a small but significant discount to anti-TNF drugs. But even a cost savings probably won’t be enough early on to knock the anti-TNFs from their established RA perch, she said.

Dr. Kremer said that he has received research support from and has been a consultant to Pfizer and several other drugs companies. Dr. McInnes said that he has received research support from and has been a consultant to and speaker for Pfizer and several other drug companies. Dr. Fleischmann said that he has received research support from and has been a consultant to Pfizer and several other drug companies. Dr. Borde said that she had no disclosures.

*New information about Dr. Borde's title has been added to this story.

UPDATED: 06/21/2012

BERLIN – If the Food and Drug Administration follows the advice of its Arthritis Advisory Committee and approves tofacitinib as a new drug for treating rheumatoid arthritis later this summer, the oral, small-molecule drug may start to muscle in on the treatment turf now occupied by antitumor necrosis factor drugs, some experts predicted at the Annual European Congress of Rheumatology.

The attraction would be the good efficacy tofacitinib has shown in five phase III trials, a decent safety profile that looks on par with antitumor necrosis factor (TNF) drugs, and delivery as a twice-daily oral pill, a property that will give tofacitinib an edge over the anti-TNFs and other biologics that require injection or infusion.

"The fact that [tofacitinib] is oral is something of an advantage, so there will be a role for it, and it makes sense therapeutically," Dr. Joel M. Kremer said at the meeting. "But we will need to be smart" on using tofacitinib and other new drugs from the same class to treat patients with rheumatoid arthritis (RA), and their use relative to methotrexate and the biologics, said Dr. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College.

Another view was that tofacitinib will need to prove its value in larger numbers of patients, and though it will be a welcome new option – first to market from the class of Janus kinase (JAK) inhibitors – it will take its initial place post approval behind the anti-TNFs, which have more than a decade’s track record, said Dr. Iain B. McInnes in a separate talk at the meeting. Many rheumatologists "feel they will kick in after a first biologic treatment," which itself comes after first-line methotrexate, said Dr. McInnes, a rheumatologist and professor and Muirhead Chair of Medicine at the University of Glasgow, Scotland.

"The efficacy we’ve seen [from tofacitinib and other JAK inhibitors] is very encouraging, but safety will be a major driver of clinical decisions and [will] influence the order of choice. If a patient does not get an adequate response from methotrexate after 3-6 months, I would add a biologic drug, especially an anti-TNF. Inevitably, there will be less safety assurance with the new drugs. The current role for JAK inhibitors is closer to the options like abatacept, rituximab, and tocilizumab, but I think that may change" once JAK inhibitors enter routine practice, Dr. McInnes said in his talk.

"I have a lot of experience with tofacitinib, and I’m very comfortable with it; if a patient wanted this drug, I would use it," said Dr. Roy Fleischmann, who led phase II and phase III trials with tofacitinib and is codirector of rheumatology at Texas Health Presbyterian Medical Center in Dallas.

"What will practicing rheumatologists with no experience with the drug do? We’ll see what the FDA says. They might use it after methotrexate, because the data are strong. It will be up to patients: an oral drug or an injected one."

Pfizer, the company developing tofacitinib, reported data from five phase III trials and safety experience in about 4,800 patients to the FDA Advisory Committee in May. And four of the five trials examined use of the drug in RA patients as monotherapy; in combination with methotrexate; in combination with background methotrexate in patients who failed to respond to an anti-TNF drug; and in combination with a background disease modifying antirheumatic drug. The fifth study, a 2-year trial that so far has reported results from an interim, 1-year analysis only, examined tofacitinib’s ability when used in combination with methotrexate to stop radiographic progression of joint damage, compared with methotrexate alone.

Results from across the studies showed consistent efficacy, including inhibition of radiographic progression that significantly surpassed placebo patients, and a "consistent side effect profile," Dr. Kremer said. "I consider it on the same shelf for potential infections and adverse events as the [already approved] biologics," he said in an interview. He said he would shy away from prescribing tofacitinib, or any biologic, to patients who get frequent pneumonia, cellulitis, or other infections.

Perceived safety will likely be the major driver – or impediment – for use of tofacitinib during the first year or 2 after its approval, predicted Madhuri Borde, Ph.D., director of the immune and inflammatory disorders group of Decision Resources, a pharmaceutical-market consulting company in Burlington, Mass. In mid-May, Dr. Borde presented 52 U.S. rheumatologists with active RA practices the same tofacitinib data that the FDA Advisory Committee saw and she asked the rheumatologists what they thought of the drug and how they might use it soon after it hit the U.S. market.*

The results showed that rheumatologists were impressed by the efficacy results, saw safety as being similar to anti-TNF drugs, and mostly saw tofacitinib currently as a drug they would use when RA patients don’t respond to an anti-TNF agent. "For physicians, it boils down to their comfort with the safety profile," she said in an interview, and they think safety is still a little uncertain.

Although Dr. Borde conceded that "patients are wary of injections" and that oral dosing is an attractive option for many patients, physician uncertainty about safety will generally trump that. "I think safety concerns will drive caution in using tofacitinib," at least during the first couple of years on the market, until a higher comfort level is reached. It’s likely that in an effort to stimulate interest in the drug, Pfizer will price it aggressively, at a small but significant discount to anti-TNF drugs. But even a cost savings probably won’t be enough early on to knock the anti-TNFs from their established RA perch, she said.

Dr. Kremer said that he has received research support from and has been a consultant to Pfizer and several other drugs companies. Dr. McInnes said that he has received research support from and has been a consultant to and speaker for Pfizer and several other drug companies. Dr. Fleischmann said that he has received research support from and has been a consultant to Pfizer and several other drug companies. Dr. Borde said that she had no disclosures.

*New information about Dr. Borde's title has been added to this story.

UPDATED: 06/21/2012

BERLIN – If the Food and Drug Administration follows the advice of its Arthritis Advisory Committee and approves tofacitinib as a new drug for treating rheumatoid arthritis later this summer, the oral, small-molecule drug may start to muscle in on the treatment turf now occupied by antitumor necrosis factor drugs, some experts predicted at the Annual European Congress of Rheumatology.

The attraction would be the good efficacy tofacitinib has shown in five phase III trials, a decent safety profile that looks on par with antitumor necrosis factor (TNF) drugs, and delivery as a twice-daily oral pill, a property that will give tofacitinib an edge over the anti-TNFs and other biologics that require injection or infusion.

"The fact that [tofacitinib] is oral is something of an advantage, so there will be a role for it, and it makes sense therapeutically," Dr. Joel M. Kremer said at the meeting. "But we will need to be smart" on using tofacitinib and other new drugs from the same class to treat patients with rheumatoid arthritis (RA), and their use relative to methotrexate and the biologics, said Dr. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College.

Another view was that tofacitinib will need to prove its value in larger numbers of patients, and though it will be a welcome new option – first to market from the class of Janus kinase (JAK) inhibitors – it will take its initial place post approval behind the anti-TNFs, which have more than a decade’s track record, said Dr. Iain B. McInnes in a separate talk at the meeting. Many rheumatologists "feel they will kick in after a first biologic treatment," which itself comes after first-line methotrexate, said Dr. McInnes, a rheumatologist and professor and Muirhead Chair of Medicine at the University of Glasgow, Scotland.

"The efficacy we’ve seen [from tofacitinib and other JAK inhibitors] is very encouraging, but safety will be a major driver of clinical decisions and [will] influence the order of choice. If a patient does not get an adequate response from methotrexate after 3-6 months, I would add a biologic drug, especially an anti-TNF. Inevitably, there will be less safety assurance with the new drugs. The current role for JAK inhibitors is closer to the options like abatacept, rituximab, and tocilizumab, but I think that may change" once JAK inhibitors enter routine practice, Dr. McInnes said in his talk.

"I have a lot of experience with tofacitinib, and I’m very comfortable with it; if a patient wanted this drug, I would use it," said Dr. Roy Fleischmann, who led phase II and phase III trials with tofacitinib and is codirector of rheumatology at Texas Health Presbyterian Medical Center in Dallas.

"What will practicing rheumatologists with no experience with the drug do? We’ll see what the FDA says. They might use it after methotrexate, because the data are strong. It will be up to patients: an oral drug or an injected one."

Pfizer, the company developing tofacitinib, reported data from five phase III trials and safety experience in about 4,800 patients to the FDA Advisory Committee in May. And four of the five trials examined use of the drug in RA patients as monotherapy; in combination with methotrexate; in combination with background methotrexate in patients who failed to respond to an anti-TNF drug; and in combination with a background disease modifying antirheumatic drug. The fifth study, a 2-year trial that so far has reported results from an interim, 1-year analysis only, examined tofacitinib’s ability when used in combination with methotrexate to stop radiographic progression of joint damage, compared with methotrexate alone.

Results from across the studies showed consistent efficacy, including inhibition of radiographic progression that significantly surpassed placebo patients, and a "consistent side effect profile," Dr. Kremer said. "I consider it on the same shelf for potential infections and adverse events as the [already approved] biologics," he said in an interview. He said he would shy away from prescribing tofacitinib, or any biologic, to patients who get frequent pneumonia, cellulitis, or other infections.

Perceived safety will likely be the major driver – or impediment – for use of tofacitinib during the first year or 2 after its approval, predicted Madhuri Borde, Ph.D., director of the immune and inflammatory disorders group of Decision Resources, a pharmaceutical-market consulting company in Burlington, Mass. In mid-May, Dr. Borde presented 52 U.S. rheumatologists with active RA practices the same tofacitinib data that the FDA Advisory Committee saw and she asked the rheumatologists what they thought of the drug and how they might use it soon after it hit the U.S. market.*

The results showed that rheumatologists were impressed by the efficacy results, saw safety as being similar to anti-TNF drugs, and mostly saw tofacitinib currently as a drug they would use when RA patients don’t respond to an anti-TNF agent. "For physicians, it boils down to their comfort with the safety profile," she said in an interview, and they think safety is still a little uncertain.

Although Dr. Borde conceded that "patients are wary of injections" and that oral dosing is an attractive option for many patients, physician uncertainty about safety will generally trump that. "I think safety concerns will drive caution in using tofacitinib," at least during the first couple of years on the market, until a higher comfort level is reached. It’s likely that in an effort to stimulate interest in the drug, Pfizer will price it aggressively, at a small but significant discount to anti-TNF drugs. But even a cost savings probably won’t be enough early on to knock the anti-TNFs from their established RA perch, she said.

Dr. Kremer said that he has received research support from and has been a consultant to Pfizer and several other drugs companies. Dr. McInnes said that he has received research support from and has been a consultant to and speaker for Pfizer and several other drug companies. Dr. Fleischmann said that he has received research support from and has been a consultant to Pfizer and several other drug companies. Dr. Borde said that she had no disclosures.

*New information about Dr. Borde's title has been added to this story.

BERLIN – Patients with at least three erosive joints in their hands and feet have rheumatoid arthritis regardless of whatever other signs and symptoms they may or may not have, according to a task force of the American College of Rheumatology and the European League Against Rheumatism (Ann. Rheum. Dis. 2012;71[Suppl3]:25).

This unanimous decision from the 18-member international task force closes the circle for redefining the classification of rheumatoid arthritis patients, a process that began with the 2010 release of a new signs and symptoms–driven rheumatoid arthritis (RA) classification that had no role for radiographic evidence of joint erosions (Arthritis Rheum. 2010;62:2569-81).

Although "radiographs are not required in the ACR/EULAR classification criteria, the presence of typical erosions allows classification of RA even without fulfillment of the [2010] scoring system," task force leader Dr. Désirée van der Heijde said at the meeting. "Radiographs should be taken in an unclassified patient in whom long-standing, inactive disease is suspected, and is likely misclassified," said Dr. van der Heijde, professor rheumatology at Leiden (the Netherlands) University Medical Center. Another common scenario is when a radiograph already exists for a patient who might have early arthritis because it was taken before rheumatologic referral.

The key premise of the new erosive-joint classification was that because radiographs alone could classify a patient as having RA, the erosive joint criteria had to be very specific and produce a minimal number of false positives. Lack of sensitivity was not an issue, as patients could also be classified with RA by the 2010 criteria.

To get a sense of how many erosive joints are needed to produce a reliable identification of RA, the task force studied data collected from two early-arthritis groups, the Early Arthritis Cohort assembled in Leiden with 902 patients, and the Etude et Suivi des Polyarthrites Indifferenciées Récentes (ESPOIR) cohort assembled in Montpellier, France with 811 patients. The task force focused on the subgroup of people in either cohort who did not meet the 2010 classification criteria for RA, and examined the link between various numbers of erosive joints in these people and the incidence of three outcomes the task force considered pathognomonic for RA: on methotrexate treatment after 1 year, on treatment with any disease-modifying antirheumatic drug after 1 year, or disease persistence for 5 years. They found that all three outcomes occurred at similar rates.

In the ESPOIR cohort, with the end point of 5-year disease persistence, people with at least three erosive joints developed RA with a specificity of 91% and a sensitivity of 24%. (An erosive joint was any hand or foot joint with at least one radiographic erosion visible as a cortical break.) In contrast, a threshold of at least two erosive joints carried a specificity of 82% – putting it below the 90% the task force sought – and a sensitivity of 30%. In the Leiden cohort, three or more erosive joints had a sensitivity of 95% and a sensitivity of 15%, while two or more joints was 91% specific and 20% sensitive.

"Some rheumatologists might be surprised [at the need for three erosive joints] because they think that just one erosion is very specific for RA. We showed that one erosion is not specific; you really need more to be very specific for RA," she said in an interview. "After we saw the data it was very clear to us that three would be the right cutoff. It was a unanimous decision."

It also turned out that a criterion of three or more erosive joints kept a lid on the number of positive classifications. In the Leiden cohort, 31 (10%) of the 308 enrollees who did not meet the 2010 clinical criteria met the radiographic threshold; in the ESPOIR cohort, 18 (12%) of 147 had at least three erosive joints.

"There will not be many patients who get classified," based on their erosive joints, she noted. Despite that, "it’s very important to have this definition, because many people were asking for it. It’s important to have a clear definition. And it’s important for patients who do not meet the classification criteria but have several erosions."

"Erosions are the hallmark of RA; if patients have erosions they don’t need anything else," commented Dr. Alan Silman, medical director of Arthritis Research UK in Chesterfield, England. The new findings show "there are very few people with RA who just have erosions. The results support the classification criteria," by showing that the 2010 criteria capture roughly 90% of all RA patients, he said in an interview.

Dr. van der Heijde and Dr. Silman said that they had no disclosures.

BERLIN – Patients with at least three erosive joints in their hands and feet have rheumatoid arthritis regardless of whatever other signs and symptoms they may or may not have, according to a task force of the American College of Rheumatology and the European League Against Rheumatism (Ann. Rheum. Dis. 2012;71[Suppl3]:25).

This unanimous decision from the 18-member international task force closes the circle for redefining the classification of rheumatoid arthritis patients, a process that began with the 2010 release of a new signs and symptoms–driven rheumatoid arthritis (RA) classification that had no role for radiographic evidence of joint erosions (Arthritis Rheum. 2010;62:2569-81).

Although "radiographs are not required in the ACR/EULAR classification criteria, the presence of typical erosions allows classification of RA even without fulfillment of the [2010] scoring system," task force leader Dr. Désirée van der Heijde said at the meeting. "Radiographs should be taken in an unclassified patient in whom long-standing, inactive disease is suspected, and is likely misclassified," said Dr. van der Heijde, professor rheumatology at Leiden (the Netherlands) University Medical Center. Another common scenario is when a radiograph already exists for a patient who might have early arthritis because it was taken before rheumatologic referral.

The key premise of the new erosive-joint classification was that because radiographs alone could classify a patient as having RA, the erosive joint criteria had to be very specific and produce a minimal number of false positives. Lack of sensitivity was not an issue, as patients could also be classified with RA by the 2010 criteria.

To get a sense of how many erosive joints are needed to produce a reliable identification of RA, the task force studied data collected from two early-arthritis groups, the Early Arthritis Cohort assembled in Leiden with 902 patients, and the Etude et Suivi des Polyarthrites Indifferenciées Récentes (ESPOIR) cohort assembled in Montpellier, France with 811 patients. The task force focused on the subgroup of people in either cohort who did not meet the 2010 classification criteria for RA, and examined the link between various numbers of erosive joints in these people and the incidence of three outcomes the task force considered pathognomonic for RA: on methotrexate treatment after 1 year, on treatment with any disease-modifying antirheumatic drug after 1 year, or disease persistence for 5 years. They found that all three outcomes occurred at similar rates.

In the ESPOIR cohort, with the end point of 5-year disease persistence, people with at least three erosive joints developed RA with a specificity of 91% and a sensitivity of 24%. (An erosive joint was any hand or foot joint with at least one radiographic erosion visible as a cortical break.) In contrast, a threshold of at least two erosive joints carried a specificity of 82% – putting it below the 90% the task force sought – and a sensitivity of 30%. In the Leiden cohort, three or more erosive joints had a sensitivity of 95% and a sensitivity of 15%, while two or more joints was 91% specific and 20% sensitive.

"Some rheumatologists might be surprised [at the need for three erosive joints] because they think that just one erosion is very specific for RA. We showed that one erosion is not specific; you really need more to be very specific for RA," she said in an interview. "After we saw the data it was very clear to us that three would be the right cutoff. It was a unanimous decision."

It also turned out that a criterion of three or more erosive joints kept a lid on the number of positive classifications. In the Leiden cohort, 31 (10%) of the 308 enrollees who did not meet the 2010 clinical criteria met the radiographic threshold; in the ESPOIR cohort, 18 (12%) of 147 had at least three erosive joints.

"There will not be many patients who get classified," based on their erosive joints, she noted. Despite that, "it’s very important to have this definition, because many people were asking for it. It’s important to have a clear definition. And it’s important for patients who do not meet the classification criteria but have several erosions."

"Erosions are the hallmark of RA; if patients have erosions they don’t need anything else," commented Dr. Alan Silman, medical director of Arthritis Research UK in Chesterfield, England. The new findings show "there are very few people with RA who just have erosions. The results support the classification criteria," by showing that the 2010 criteria capture roughly 90% of all RA patients, he said in an interview.

Dr. van der Heijde and Dr. Silman said that they had no disclosures.

BERLIN – Patients with at least three erosive joints in their hands and feet have rheumatoid arthritis regardless of whatever other signs and symptoms they may or may not have, according to a task force of the American College of Rheumatology and the European League Against Rheumatism (Ann. Rheum. Dis. 2012;71[Suppl3]:25).

This unanimous decision from the 18-member international task force closes the circle for redefining the classification of rheumatoid arthritis patients, a process that began with the 2010 release of a new signs and symptoms–driven rheumatoid arthritis (RA) classification that had no role for radiographic evidence of joint erosions (Arthritis Rheum. 2010;62:2569-81).

Although "radiographs are not required in the ACR/EULAR classification criteria, the presence of typical erosions allows classification of RA even without fulfillment of the [2010] scoring system," task force leader Dr. Désirée van der Heijde said at the meeting. "Radiographs should be taken in an unclassified patient in whom long-standing, inactive disease is suspected, and is likely misclassified," said Dr. van der Heijde, professor rheumatology at Leiden (the Netherlands) University Medical Center. Another common scenario is when a radiograph already exists for a patient who might have early arthritis because it was taken before rheumatologic referral.

The key premise of the new erosive-joint classification was that because radiographs alone could classify a patient as having RA, the erosive joint criteria had to be very specific and produce a minimal number of false positives. Lack of sensitivity was not an issue, as patients could also be classified with RA by the 2010 criteria.

To get a sense of how many erosive joints are needed to produce a reliable identification of RA, the task force studied data collected from two early-arthritis groups, the Early Arthritis Cohort assembled in Leiden with 902 patients, and the Etude et Suivi des Polyarthrites Indifferenciées Récentes (ESPOIR) cohort assembled in Montpellier, France with 811 patients. The task force focused on the subgroup of people in either cohort who did not meet the 2010 classification criteria for RA, and examined the link between various numbers of erosive joints in these people and the incidence of three outcomes the task force considered pathognomonic for RA: on methotrexate treatment after 1 year, on treatment with any disease-modifying antirheumatic drug after 1 year, or disease persistence for 5 years. They found that all three outcomes occurred at similar rates.

In the ESPOIR cohort, with the end point of 5-year disease persistence, people with at least three erosive joints developed RA with a specificity of 91% and a sensitivity of 24%. (An erosive joint was any hand or foot joint with at least one radiographic erosion visible as a cortical break.) In contrast, a threshold of at least two erosive joints carried a specificity of 82% – putting it below the 90% the task force sought – and a sensitivity of 30%. In the Leiden cohort, three or more erosive joints had a sensitivity of 95% and a sensitivity of 15%, while two or more joints was 91% specific and 20% sensitive.

"Some rheumatologists might be surprised [at the need for three erosive joints] because they think that just one erosion is very specific for RA. We showed that one erosion is not specific; you really need more to be very specific for RA," she said in an interview. "After we saw the data it was very clear to us that three would be the right cutoff. It was a unanimous decision."

It also turned out that a criterion of three or more erosive joints kept a lid on the number of positive classifications. In the Leiden cohort, 31 (10%) of the 308 enrollees who did not meet the 2010 clinical criteria met the radiographic threshold; in the ESPOIR cohort, 18 (12%) of 147 had at least three erosive joints.

"There will not be many patients who get classified," based on their erosive joints, she noted. Despite that, "it’s very important to have this definition, because many people were asking for it. It’s important to have a clear definition. And it’s important for patients who do not meet the classification criteria but have several erosions."

"Erosions are the hallmark of RA; if patients have erosions they don’t need anything else," commented Dr. Alan Silman, medical director of Arthritis Research UK in Chesterfield, England. The new findings show "there are very few people with RA who just have erosions. The results support the classification criteria," by showing that the 2010 criteria capture roughly 90% of all RA patients, he said in an interview.

Dr. van der Heijde and Dr. Silman said that they had no disclosures.

PHILADELPHIA – The practice of psychotherapy by psychiatrists dropped by 20 percentage points from 2002 to 2010, in large part because of low reimbursement levels and the inability of many patients to afford psychotherapy sessions out of pocket, based on results from a 2010 survey completed by 394 practicing psychiatrists.

The survey results did not address the extent to which the psychotherapy that psychiatrists no longer provide has been replaced by sessions with other types of psychotherapy providers, Joyce C. West, Ph.D., said at the annual meeting of the American Psychiatric Association. "The trend is for psychiatrists to be team leaders" in caring for psychiatric patients, and for psychiatrists to "make referrals for psychotherapy to other team members," said Dr. West, director of policy research at the American Psychiatric Institute for Research and Education in Arlington, Va.

Mitchel L. Zoler/IMNG Medical Media

In contrast, during the same period, psychiatrists embraced pharmacotherapy more tightly, with the use of drug therapy rising to 89% of responding psychiatrists in 2010, up from 81% in 2002 and from 54% in 1988.

Growth in the availability of psychotherapy from nonpsychiatrists helped keep psychotherapy available. "There clearly is a strong evidence base for [the efficacy of] psychotherapy, and patients with resources [to pay for it themselves] are more likely to want psychotherapy," she noted.

The survey results and other recent psychotherapy assessments document a shift in who delivers psychotherapy. "The percentage of the population receiving psychotherapy in a year has not significantly lowered," at 3.18% of the U.S. population in 2007, essentially unchanged from the 3.37% rate in 1998. "However, there was a decline in psychiatrists providing psychotherapy; more patients of psychiatrists received medications, rising from 44% in 2002 to 57% in 2010. It appears that psychotherapy increasingly shifted away from psychiatrists, while other professions provided it," said Dr. John Christopher Perry, a coinvestigator with Dr. West on the survey, and a professor of psychiatry at McGill University in Montreal.

Is it okay if a steady number of patients has access to psychotherapy, but that it increasingly comes from nonpsychiatrists? "Psychotherapy is a core discipline in psychiatry, but it is shared with other professions. Understanding the mind and body, and understanding how intervening with one affects the other is an approach that is unique to psychiatry.

"If psychiatrists shift to mostly being diagnosticians and prescribers, we will lose this and become less knowledgeable about understanding and helping people. When a psychiatrist only manages medications and someone else provides psychotherapy, it limits the view of a patient’s symptoms, and may lead to overprescribing. When the psychiatrist is also the therapist, there is better opportunity to deal with life stress, coping, and distress without relying primarily or solely on prescribing," said Dr. Perry, who is also director of psychotherapy research at Jewish General Hospital in Montreal.

To examine how psychiatrists used psychotherapy in 2010, Dr. West, Dr. Perry, and their associates sent a 36-item questionnaire on the subject to a random sample of 3,000 members of the American Psychiatric Association, excluding medical students and residents. The researchers received completed surveys from 394 practicing psychiatrists. The respondents averaged 54 years old, two-thirds were men, 83% were white, and half were in private practice. Each psychiatrist saw an average of 42 patients in a typical week.

When asked how they treated patients during their most recent typical week, 48% said that they used psychotherapy and 89% said that they used pharmacotherapy – either in combination or as monotherapy – in an analysis that weighted responses based on the number of patients each psychiatrist treated. For psychotherapy, the 48% prevalence of use compared with 68% in a 2002 survey and 72% in a 1988 survey. The drug therapy rate of 89% in 2010 compared with 81% in 2002 and 54% in 1988.

When asked what barriers they encountered when performing psychotherapy, 80% of responding psychiatrists cited financial barriers, and 72% noted administrative barriers. Financial barriers included an inability of patients to afford psychotherapy sessions themselves, and low reimbursement rates from third-party payers. Administrative barriers included dealing with insurance companies and writing treatment notes.

Half the responding psychiatrists also cited pressure to treat psychotherapy patients in shorter sessions and with fewer sessions, and 48% reported pressure to spend more time focused on diagnosis and on pharmacologic consultations. Just over half the respondents said their practice of psychotherapy would increase if the reimbursement level approached that for pharmacotherapy.

Responding psychiatrists found pharmacotherapy somewhat more effective, with 87% saying they were satisfied with the efficacy or helpfulness of pharmacotherapy, compared with 76% who had the same assessment of psychotherapy.

Reimbursement patterns for psychotherapy are in flux, noted Dr. Perry. In both the United States and Canada, health care payers "tend to undervalue psychotherapy relative to consultation and medication management." As a consequence, "more and more providers do not accept insurance or avoid certain types of insurance such as Medicare and Medicaid" for psychotherapy. Another reimbursement issue is payers’ deciding "who gets how much psychotherapy," Dr. Perry said. "I pray that a creative group of psychiatrists, health economists, and public health people, along with some government input, comes up with alternatives.

"Clearly, no one [reimbursement] system will work for every patient who needs psychotherapy."

Dr. West and Dr. Perry said they had no disclosures.

PHILADELPHIA – The practice of psychotherapy by psychiatrists dropped by 20 percentage points from 2002 to 2010, in large part because of low reimbursement levels and the inability of many patients to afford psychotherapy sessions out of pocket, based on results from a 2010 survey completed by 394 practicing psychiatrists.

The survey results did not address the extent to which the psychotherapy that psychiatrists no longer provide has been replaced by sessions with other types of psychotherapy providers, Joyce C. West, Ph.D., said at the annual meeting of the American Psychiatric Association. "The trend is for psychiatrists to be team leaders" in caring for psychiatric patients, and for psychiatrists to "make referrals for psychotherapy to other team members," said Dr. West, director of policy research at the American Psychiatric Institute for Research and Education in Arlington, Va.

Mitchel L. Zoler/IMNG Medical Media

In contrast, during the same period, psychiatrists embraced pharmacotherapy more tightly, with the use of drug therapy rising to 89% of responding psychiatrists in 2010, up from 81% in 2002 and from 54% in 1988.

Growth in the availability of psychotherapy from nonpsychiatrists helped keep psychotherapy available. "There clearly is a strong evidence base for [the efficacy of] psychotherapy, and patients with resources [to pay for it themselves] are more likely to want psychotherapy," she noted.

The survey results and other recent psychotherapy assessments document a shift in who delivers psychotherapy. "The percentage of the population receiving psychotherapy in a year has not significantly lowered," at 3.18% of the U.S. population in 2007, essentially unchanged from the 3.37% rate in 1998. "However, there was a decline in psychiatrists providing psychotherapy; more patients of psychiatrists received medications, rising from 44% in 2002 to 57% in 2010. It appears that psychotherapy increasingly shifted away from psychiatrists, while other professions provided it," said Dr. John Christopher Perry, a coinvestigator with Dr. West on the survey, and a professor of psychiatry at McGill University in Montreal.

Is it okay if a steady number of patients has access to psychotherapy, but that it increasingly comes from nonpsychiatrists? "Psychotherapy is a core discipline in psychiatry, but it is shared with other professions. Understanding the mind and body, and understanding how intervening with one affects the other is an approach that is unique to psychiatry.

"If psychiatrists shift to mostly being diagnosticians and prescribers, we will lose this and become less knowledgeable about understanding and helping people. When a psychiatrist only manages medications and someone else provides psychotherapy, it limits the view of a patient’s symptoms, and may lead to overprescribing. When the psychiatrist is also the therapist, there is better opportunity to deal with life stress, coping, and distress without relying primarily or solely on prescribing," said Dr. Perry, who is also director of psychotherapy research at Jewish General Hospital in Montreal.

To examine how psychiatrists used psychotherapy in 2010, Dr. West, Dr. Perry, and their associates sent a 36-item questionnaire on the subject to a random sample of 3,000 members of the American Psychiatric Association, excluding medical students and residents. The researchers received completed surveys from 394 practicing psychiatrists. The respondents averaged 54 years old, two-thirds were men, 83% were white, and half were in private practice. Each psychiatrist saw an average of 42 patients in a typical week.

When asked how they treated patients during their most recent typical week, 48% said that they used psychotherapy and 89% said that they used pharmacotherapy – either in combination or as monotherapy – in an analysis that weighted responses based on the number of patients each psychiatrist treated. For psychotherapy, the 48% prevalence of use compared with 68% in a 2002 survey and 72% in a 1988 survey. The drug therapy rate of 89% in 2010 compared with 81% in 2002 and 54% in 1988.

When asked what barriers they encountered when performing psychotherapy, 80% of responding psychiatrists cited financial barriers, and 72% noted administrative barriers. Financial barriers included an inability of patients to afford psychotherapy sessions themselves, and low reimbursement rates from third-party payers. Administrative barriers included dealing with insurance companies and writing treatment notes.

Half the responding psychiatrists also cited pressure to treat psychotherapy patients in shorter sessions and with fewer sessions, and 48% reported pressure to spend more time focused on diagnosis and on pharmacologic consultations. Just over half the respondents said their practice of psychotherapy would increase if the reimbursement level approached that for pharmacotherapy.

Responding psychiatrists found pharmacotherapy somewhat more effective, with 87% saying they were satisfied with the efficacy or helpfulness of pharmacotherapy, compared with 76% who had the same assessment of psychotherapy.

Reimbursement patterns for psychotherapy are in flux, noted Dr. Perry. In both the United States and Canada, health care payers "tend to undervalue psychotherapy relative to consultation and medication management." As a consequence, "more and more providers do not accept insurance or avoid certain types of insurance such as Medicare and Medicaid" for psychotherapy. Another reimbursement issue is payers’ deciding "who gets how much psychotherapy," Dr. Perry said. "I pray that a creative group of psychiatrists, health economists, and public health people, along with some government input, comes up with alternatives.

"Clearly, no one [reimbursement] system will work for every patient who needs psychotherapy."

Dr. West and Dr. Perry said they had no disclosures.

PHILADELPHIA – The practice of psychotherapy by psychiatrists dropped by 20 percentage points from 2002 to 2010, in large part because of low reimbursement levels and the inability of many patients to afford psychotherapy sessions out of pocket, based on results from a 2010 survey completed by 394 practicing psychiatrists.

The survey results did not address the extent to which the psychotherapy that psychiatrists no longer provide has been replaced by sessions with other types of psychotherapy providers, Joyce C. West, Ph.D., said at the annual meeting of the American Psychiatric Association. "The trend is for psychiatrists to be team leaders" in caring for psychiatric patients, and for psychiatrists to "make referrals for psychotherapy to other team members," said Dr. West, director of policy research at the American Psychiatric Institute for Research and Education in Arlington, Va.

Mitchel L. Zoler/IMNG Medical Media

In contrast, during the same period, psychiatrists embraced pharmacotherapy more tightly, with the use of drug therapy rising to 89% of responding psychiatrists in 2010, up from 81% in 2002 and from 54% in 1988.

Growth in the availability of psychotherapy from nonpsychiatrists helped keep psychotherapy available. "There clearly is a strong evidence base for [the efficacy of] psychotherapy, and patients with resources [to pay for it themselves] are more likely to want psychotherapy," she noted.

The survey results and other recent psychotherapy assessments document a shift in who delivers psychotherapy. "The percentage of the population receiving psychotherapy in a year has not significantly lowered," at 3.18% of the U.S. population in 2007, essentially unchanged from the 3.37% rate in 1998. "However, there was a decline in psychiatrists providing psychotherapy; more patients of psychiatrists received medications, rising from 44% in 2002 to 57% in 2010. It appears that psychotherapy increasingly shifted away from psychiatrists, while other professions provided it," said Dr. John Christopher Perry, a coinvestigator with Dr. West on the survey, and a professor of psychiatry at McGill University in Montreal.

Is it okay if a steady number of patients has access to psychotherapy, but that it increasingly comes from nonpsychiatrists? "Psychotherapy is a core discipline in psychiatry, but it is shared with other professions. Understanding the mind and body, and understanding how intervening with one affects the other is an approach that is unique to psychiatry.

"If psychiatrists shift to mostly being diagnosticians and prescribers, we will lose this and become less knowledgeable about understanding and helping people. When a psychiatrist only manages medications and someone else provides psychotherapy, it limits the view of a patient’s symptoms, and may lead to overprescribing. When the psychiatrist is also the therapist, there is better opportunity to deal with life stress, coping, and distress without relying primarily or solely on prescribing," said Dr. Perry, who is also director of psychotherapy research at Jewish General Hospital in Montreal.

To examine how psychiatrists used psychotherapy in 2010, Dr. West, Dr. Perry, and their associates sent a 36-item questionnaire on the subject to a random sample of 3,000 members of the American Psychiatric Association, excluding medical students and residents. The researchers received completed surveys from 394 practicing psychiatrists. The respondents averaged 54 years old, two-thirds were men, 83% were white, and half were in private practice. Each psychiatrist saw an average of 42 patients in a typical week.

When asked how they treated patients during their most recent typical week, 48% said that they used psychotherapy and 89% said that they used pharmacotherapy – either in combination or as monotherapy – in an analysis that weighted responses based on the number of patients each psychiatrist treated. For psychotherapy, the 48% prevalence of use compared with 68% in a 2002 survey and 72% in a 1988 survey. The drug therapy rate of 89% in 2010 compared with 81% in 2002 and 54% in 1988.

When asked what barriers they encountered when performing psychotherapy, 80% of responding psychiatrists cited financial barriers, and 72% noted administrative barriers. Financial barriers included an inability of patients to afford psychotherapy sessions themselves, and low reimbursement rates from third-party payers. Administrative barriers included dealing with insurance companies and writing treatment notes.

Half the responding psychiatrists also cited pressure to treat psychotherapy patients in shorter sessions and with fewer sessions, and 48% reported pressure to spend more time focused on diagnosis and on pharmacologic consultations. Just over half the respondents said their practice of psychotherapy would increase if the reimbursement level approached that for pharmacotherapy.

Responding psychiatrists found pharmacotherapy somewhat more effective, with 87% saying they were satisfied with the efficacy or helpfulness of pharmacotherapy, compared with 76% who had the same assessment of psychotherapy.

Reimbursement patterns for psychotherapy are in flux, noted Dr. Perry. In both the United States and Canada, health care payers "tend to undervalue psychotherapy relative to consultation and medication management." As a consequence, "more and more providers do not accept insurance or avoid certain types of insurance such as Medicare and Medicaid" for psychotherapy. Another reimbursement issue is payers’ deciding "who gets how much psychotherapy," Dr. Perry said. "I pray that a creative group of psychiatrists, health economists, and public health people, along with some government input, comes up with alternatives.

"Clearly, no one [reimbursement] system will work for every patient who needs psychotherapy."

Dr. West and Dr. Perry said they had no disclosures.

SAN DIEGO – Changing the acid content of the gastrointestinal tract may reduce the risk of developing pouchitis following ileal pouch anal anastomosis, based on a review of 85 patients at one U.S. center.

After patients underwent ileal pouch anal anastomosis (IPAA) for ulcerative colitis, those who did not develop pouchitis used a proton pump inhibitor (PPI) or histamine₂ (H₂) blocker on a daily basis significantly more often than did patients who developed pouchitis during follow-up, Dr. Lisa S. Poritz said at the annual Digestive Disease Week.

Patients who did not develop pouchitis also regularly used an antacid significantly more often than did those with pouchitis during follow-up, but "occasional" use of a PPI or H₂ blocker showed no statistically significant association with reduced pouchitis incidence, said Dr. Poritz, a colon and rectal surgeon at Pennsylvania State University, Hershey.

Pouchitis is the most common complication of IPAA, occurring in about half of these patients, and chronic pouchitis develops in 5%-19% of them, Dr. Poritz said. Pouchitis produces urgency, bloody bowel movements, and abdominal pain.

IPAA patients who require chronic antibiotic treatment for pouchitis are the subgroup with the best chance to benefit from daily treatment to stop or neutralize acid secretion, a strategy that would "hopefully get them off chronic antibiotics," she said.

The study reviewed ulcerative colitis patients from the Penn State Familial IBD Registry who had undergone IPAA and had at least 2 subsequent years of follow-up. In all, 45 patients developed no pouchitis, and 40 had pouchitis. The registry data showed no demographic or clinical differences between the two subgroups.

The researchers limited their analysis of acid treatment associations to the subgroup of patients for whom data were available. In all, 15 of 30 patients who had no pouchitis following IPAA and 5 of 35 who developed pouchitis received daily treatment with a PPI or H₂ blocker, a statistically significant difference. And 12 of 21 patients with no pouchitis took an antacid more than once a week, compared with 3 of 25 patients who developed pouchitis, also a statistically significant difference.

The analysis showed very similar usage rates among the pouchitis and no-pouchitis subgroups for a variety of other agents that could potentially influence this complication, including probiotics, NSAIDs, fiber supplements, antidiarrheal drugs, and immunosuppressive drugs.

The treatment effects of a PPI or H₂ blocker on the incidence of pouchitis may be mediated by changes in fecal flora, but clear evidence for the mechanism of action will require further study, she said.

Dr. Poritz said that she had no disclosures.

SAN DIEGO – Changing the acid content of the gastrointestinal tract may reduce the risk of developing pouchitis following ileal pouch anal anastomosis, based on a review of 85 patients at one U.S. center.

After patients underwent ileal pouch anal anastomosis (IPAA) for ulcerative colitis, those who did not develop pouchitis used a proton pump inhibitor (PPI) or histamine₂ (H₂) blocker on a daily basis significantly more often than did patients who developed pouchitis during follow-up, Dr. Lisa S. Poritz said at the annual Digestive Disease Week.

Patients who did not develop pouchitis also regularly used an antacid significantly more often than did those with pouchitis during follow-up, but "occasional" use of a PPI or H₂ blocker showed no statistically significant association with reduced pouchitis incidence, said Dr. Poritz, a colon and rectal surgeon at Pennsylvania State University, Hershey.

Pouchitis is the most common complication of IPAA, occurring in about half of these patients, and chronic pouchitis develops in 5%-19% of them, Dr. Poritz said. Pouchitis produces urgency, bloody bowel movements, and abdominal pain.

IPAA patients who require chronic antibiotic treatment for pouchitis are the subgroup with the best chance to benefit from daily treatment to stop or neutralize acid secretion, a strategy that would "hopefully get them off chronic antibiotics," she said.

The study reviewed ulcerative colitis patients from the Penn State Familial IBD Registry who had undergone IPAA and had at least 2 subsequent years of follow-up. In all, 45 patients developed no pouchitis, and 40 had pouchitis. The registry data showed no demographic or clinical differences between the two subgroups.

The researchers limited their analysis of acid treatment associations to the subgroup of patients for whom data were available. In all, 15 of 30 patients who had no pouchitis following IPAA and 5 of 35 who developed pouchitis received daily treatment with a PPI or H₂ blocker, a statistically significant difference. And 12 of 21 patients with no pouchitis took an antacid more than once a week, compared with 3 of 25 patients who developed pouchitis, also a statistically significant difference.

The analysis showed very similar usage rates among the pouchitis and no-pouchitis subgroups for a variety of other agents that could potentially influence this complication, including probiotics, NSAIDs, fiber supplements, antidiarrheal drugs, and immunosuppressive drugs.

The treatment effects of a PPI or H₂ blocker on the incidence of pouchitis may be mediated by changes in fecal flora, but clear evidence for the mechanism of action will require further study, she said.

Dr. Poritz said that she had no disclosures.

SAN DIEGO – Changing the acid content of the gastrointestinal tract may reduce the risk of developing pouchitis following ileal pouch anal anastomosis, based on a review of 85 patients at one U.S. center.

After patients underwent ileal pouch anal anastomosis (IPAA) for ulcerative colitis, those who did not develop pouchitis used a proton pump inhibitor (PPI) or histamine₂ (H₂) blocker on a daily basis significantly more often than did patients who developed pouchitis during follow-up, Dr. Lisa S. Poritz said at the annual Digestive Disease Week.

Patients who did not develop pouchitis also regularly used an antacid significantly more often than did those with pouchitis during follow-up, but "occasional" use of a PPI or H₂ blocker showed no statistically significant association with reduced pouchitis incidence, said Dr. Poritz, a colon and rectal surgeon at Pennsylvania State University, Hershey.

Pouchitis is the most common complication of IPAA, occurring in about half of these patients, and chronic pouchitis develops in 5%-19% of them, Dr. Poritz said. Pouchitis produces urgency, bloody bowel movements, and abdominal pain.

IPAA patients who require chronic antibiotic treatment for pouchitis are the subgroup with the best chance to benefit from daily treatment to stop or neutralize acid secretion, a strategy that would "hopefully get them off chronic antibiotics," she said.

The study reviewed ulcerative colitis patients from the Penn State Familial IBD Registry who had undergone IPAA and had at least 2 subsequent years of follow-up. In all, 45 patients developed no pouchitis, and 40 had pouchitis. The registry data showed no demographic or clinical differences between the two subgroups.

The researchers limited their analysis of acid treatment associations to the subgroup of patients for whom data were available. In all, 15 of 30 patients who had no pouchitis following IPAA and 5 of 35 who developed pouchitis received daily treatment with a PPI or H₂ blocker, a statistically significant difference. And 12 of 21 patients with no pouchitis took an antacid more than once a week, compared with 3 of 25 patients who developed pouchitis, also a statistically significant difference.

The analysis showed very similar usage rates among the pouchitis and no-pouchitis subgroups for a variety of other agents that could potentially influence this complication, including probiotics, NSAIDs, fiber supplements, antidiarrheal drugs, and immunosuppressive drugs.

The treatment effects of a PPI or H₂ blocker on the incidence of pouchitis may be mediated by changes in fecal flora, but clear evidence for the mechanism of action will require further study, she said.

Dr. Poritz said that she had no disclosures.