Rheumatoid Arthritis

SILVER SPRING, MD. – There soon may be a new oral disease-modifying antirheumatic drug in town, the first in more than 10 years to be approved for the treatment of rheumatoid arthritis.

The drug is tofacitinib, and it is the first in a new class of agents for RA patients.

On May 9 the Food and Drug Administration’s Arthritis Advisory Committee voted 8 to 2 in favor of approving tofacitinib for RA patients who have had inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).

A small-molecule inhibitor of the Janus kinase (JAK) pathways, Pfizer’s tofacitinib blocks inflammatory cytokines that play a role in the pathogenesis of RA. If approved, tofacitinib would be the first JAK inhibitor for RA. Another JAK inhibitor, ruxolitinib (Incyte’s Jakafi) was approved to treat myelofibrosis in November.

Pfizer’s application was based on five randomized controlled phase III efficacy trials involving a total 3,315 patients. The application also included safety data for a total of 4,816 patients from the phase II and III studies, of whom 4,053 were treated for at least 6 months and 567 for more than 3 years, up to 42 months. Among the trials was one that compared tofacitinib with placebo in patients with moderate to severe RA who had incomplete responses to tumor necrosis factor (TNF) inhibitors, and four studies of patients who had inadequate responses to other DMARDs. One study included an arm with adalimumab as an active comparator, and one evaluated radiographic response. In three studies, the participants were taking background methotrexate, and in one study, tofacitinib was used as monotherapy. The studies were conducted in a total of 44 countries.

All five of the phase III studies were designed to show the superiority of 5-mg and 10-mg twice-daily doses of tofacitinib to placebo for the primary end points: a 20% or better increase in the American College of Rheumatology’s definition of improvement in the signs and symptoms of RA (ACR20), improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and a Disease Activity Score-28 (DAS28) of less than 2.6. In most of the assessments conducted at 6 and 12 months, both doses exhibited statistical superiority over placebo, with the 10-mg dose showing greater improvement than the 5-mg dose.

However, the fact that only one study evaluated radiographic evidence, which the FDA reviewers deemed inconclusive, was cause for concern for the FDA reviewers and committee members. According to the FDA’s Dr. Yongman Kim, 18% of the 278 patients on 5 mg of tofacitinib, 16% of the 290 with 10 mg of tofacitinib, and 14% of the 140 placebo patients showed an "improved" modified total sharp score (mTSS) of less than 0, suggesting it inhibited joint damage.

The FDA was also concerned about dose- and time-dependent elevations in malignancies, and particularly lymphomas, with a standardized incidence ratio of 2.35 at a median 9 months duration of exposure. Of the seven total patients who developed lymphoma, three were on 5 mg of tofacitinib, three were on 10 mg, and one was in a still-blinded arm of the trial. Overall malignancy rates increased with time, from 0.79 per 100 patient-years at 0-6 months to 1.06 at 12-18 months to 1.43 beyond 24 months.

Several of the committee members who voted in favor of tofacitinib said that they did so because they wanted a new oral option for RA patients and that they don’t anticipate any better data from clinical trials. They strongly urged postmarketing studies of both radiologic efficacy and safety. Pfizer has proposed a Risk Evaluation and Mitigation Strategy that will include, alongside labeling provisions, a Medication Guide, a "Dear Health Care Professional" letter, and routine pharmacovigilance. Additional clinical studies that are ongoing or planned include long-term extension studies to assess cardiovascular safety, serious and opportunistic infections, malignancies, and gastrointestinal perforations; studies to monitor any unidentified risks; a cholesterol kinetic study; and studies to evaluate the effect of tofacitinib on the immune response to pneumococcal and influenza vaccines as well as to further delineate the effects of tofacitinib on lymphocyte subsets.

The panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver but not at this meeting.

Martin Bermin-Gorvine of "The Pink Sheet" contributed to this story. This news service and "The Pink Sheet" are both owned by Elsevier.

SILVER SPRING, MD. – There soon may be a new oral disease-modifying antirheumatic drug in town, the first in more than 10 years to be approved for the treatment of rheumatoid arthritis.

The drug is tofacitinib, and it is the first in a new class of agents for RA patients.

On May 9 the Food and Drug Administration’s Arthritis Advisory Committee voted 8 to 2 in favor of approving tofacitinib for RA patients who have had inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).

A small-molecule inhibitor of the Janus kinase (JAK) pathways, Pfizer’s tofacitinib blocks inflammatory cytokines that play a role in the pathogenesis of RA. If approved, tofacitinib would be the first JAK inhibitor for RA. Another JAK inhibitor, ruxolitinib (Incyte’s Jakafi) was approved to treat myelofibrosis in November.

Pfizer’s application was based on five randomized controlled phase III efficacy trials involving a total 3,315 patients. The application also included safety data for a total of 4,816 patients from the phase II and III studies, of whom 4,053 were treated for at least 6 months and 567 for more than 3 years, up to 42 months. Among the trials was one that compared tofacitinib with placebo in patients with moderate to severe RA who had incomplete responses to tumor necrosis factor (TNF) inhibitors, and four studies of patients who had inadequate responses to other DMARDs. One study included an arm with adalimumab as an active comparator, and one evaluated radiographic response. In three studies, the participants were taking background methotrexate, and in one study, tofacitinib was used as monotherapy. The studies were conducted in a total of 44 countries.

All five of the phase III studies were designed to show the superiority of 5-mg and 10-mg twice-daily doses of tofacitinib to placebo for the primary end points: a 20% or better increase in the American College of Rheumatology’s definition of improvement in the signs and symptoms of RA (ACR20), improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and a Disease Activity Score-28 (DAS28) of less than 2.6. In most of the assessments conducted at 6 and 12 months, both doses exhibited statistical superiority over placebo, with the 10-mg dose showing greater improvement than the 5-mg dose.

However, the fact that only one study evaluated radiographic evidence, which the FDA reviewers deemed inconclusive, was cause for concern for the FDA reviewers and committee members. According to the FDA’s Dr. Yongman Kim, 18% of the 278 patients on 5 mg of tofacitinib, 16% of the 290 with 10 mg of tofacitinib, and 14% of the 140 placebo patients showed an "improved" modified total sharp score (mTSS) of less than 0, suggesting it inhibited joint damage.

The FDA was also concerned about dose- and time-dependent elevations in malignancies, and particularly lymphomas, with a standardized incidence ratio of 2.35 at a median 9 months duration of exposure. Of the seven total patients who developed lymphoma, three were on 5 mg of tofacitinib, three were on 10 mg, and one was in a still-blinded arm of the trial. Overall malignancy rates increased with time, from 0.79 per 100 patient-years at 0-6 months to 1.06 at 12-18 months to 1.43 beyond 24 months.

Several of the committee members who voted in favor of tofacitinib said that they did so because they wanted a new oral option for RA patients and that they don’t anticipate any better data from clinical trials. They strongly urged postmarketing studies of both radiologic efficacy and safety. Pfizer has proposed a Risk Evaluation and Mitigation Strategy that will include, alongside labeling provisions, a Medication Guide, a "Dear Health Care Professional" letter, and routine pharmacovigilance. Additional clinical studies that are ongoing or planned include long-term extension studies to assess cardiovascular safety, serious and opportunistic infections, malignancies, and gastrointestinal perforations; studies to monitor any unidentified risks; a cholesterol kinetic study; and studies to evaluate the effect of tofacitinib on the immune response to pneumococcal and influenza vaccines as well as to further delineate the effects of tofacitinib on lymphocyte subsets.

The panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver but not at this meeting.

Martin Bermin-Gorvine of "The Pink Sheet" contributed to this story. This news service and "The Pink Sheet" are both owned by Elsevier.

SILVER SPRING, MD. – There soon may be a new oral disease-modifying antirheumatic drug in town, the first in more than 10 years to be approved for the treatment of rheumatoid arthritis.

The drug is tofacitinib, and it is the first in a new class of agents for RA patients.

On May 9 the Food and Drug Administration’s Arthritis Advisory Committee voted 8 to 2 in favor of approving tofacitinib for RA patients who have had inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).

A small-molecule inhibitor of the Janus kinase (JAK) pathways, Pfizer’s tofacitinib blocks inflammatory cytokines that play a role in the pathogenesis of RA. If approved, tofacitinib would be the first JAK inhibitor for RA. Another JAK inhibitor, ruxolitinib (Incyte’s Jakafi) was approved to treat myelofibrosis in November.

Pfizer’s application was based on five randomized controlled phase III efficacy trials involving a total 3,315 patients. The application also included safety data for a total of 4,816 patients from the phase II and III studies, of whom 4,053 were treated for at least 6 months and 567 for more than 3 years, up to 42 months. Among the trials was one that compared tofacitinib with placebo in patients with moderate to severe RA who had incomplete responses to tumor necrosis factor (TNF) inhibitors, and four studies of patients who had inadequate responses to other DMARDs. One study included an arm with adalimumab as an active comparator, and one evaluated radiographic response. In three studies, the participants were taking background methotrexate, and in one study, tofacitinib was used as monotherapy. The studies were conducted in a total of 44 countries.

All five of the phase III studies were designed to show the superiority of 5-mg and 10-mg twice-daily doses of tofacitinib to placebo for the primary end points: a 20% or better increase in the American College of Rheumatology’s definition of improvement in the signs and symptoms of RA (ACR20), improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and a Disease Activity Score-28 (DAS28) of less than 2.6. In most of the assessments conducted at 6 and 12 months, both doses exhibited statistical superiority over placebo, with the 10-mg dose showing greater improvement than the 5-mg dose.

However, the fact that only one study evaluated radiographic evidence, which the FDA reviewers deemed inconclusive, was cause for concern for the FDA reviewers and committee members. According to the FDA’s Dr. Yongman Kim, 18% of the 278 patients on 5 mg of tofacitinib, 16% of the 290 with 10 mg of tofacitinib, and 14% of the 140 placebo patients showed an "improved" modified total sharp score (mTSS) of less than 0, suggesting it inhibited joint damage.

The FDA was also concerned about dose- and time-dependent elevations in malignancies, and particularly lymphomas, with a standardized incidence ratio of 2.35 at a median 9 months duration of exposure. Of the seven total patients who developed lymphoma, three were on 5 mg of tofacitinib, three were on 10 mg, and one was in a still-blinded arm of the trial. Overall malignancy rates increased with time, from 0.79 per 100 patient-years at 0-6 months to 1.06 at 12-18 months to 1.43 beyond 24 months.

Several of the committee members who voted in favor of tofacitinib said that they did so because they wanted a new oral option for RA patients and that they don’t anticipate any better data from clinical trials. They strongly urged postmarketing studies of both radiologic efficacy and safety. Pfizer has proposed a Risk Evaluation and Mitigation Strategy that will include, alongside labeling provisions, a Medication Guide, a "Dear Health Care Professional" letter, and routine pharmacovigilance. Additional clinical studies that are ongoing or planned include long-term extension studies to assess cardiovascular safety, serious and opportunistic infections, malignancies, and gastrointestinal perforations; studies to monitor any unidentified risks; a cholesterol kinetic study; and studies to evaluate the effect of tofacitinib on the immune response to pneumococcal and influenza vaccines as well as to further delineate the effects of tofacitinib on lymphocyte subsets.

The panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver but not at this meeting.

Martin Bermin-Gorvine of "The Pink Sheet" contributed to this story. This news service and "The Pink Sheet" are both owned by Elsevier.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

VICTORIA, B.C. – Physician and patient assessments of disease activity in rheumatoid arthritis show considerable disagreement that seems to be driven by subjective perceptions of pain, a study has shown.

The study involved nearly 900 patients with early rheumatoid arthritis (RA) and 100 patients with established RA in remission, all of whom had been treated only with disease-modifying antirheumatic drugs (DMARDs). Findings on physician and patient assessments of disease activity disagreed to a clinically meaningful extent roughly one-fourth to one-third of the time, based on the results of this as-yet unpublished study, reported at the annual meeting of the Canadian Rheumatology Association.

In most cases of discordance, patients rated their RA as being worse than their physicians did. Findings from additional analyses suggested that the discrepancy was largely due to subjective pain, and pain levels showed some association with cumulative RA-related joint damage.

"For a rheumatologist who is using these global assessment scores" – the patient global assessment (PtGA) and the physician global assessment (MDGA) – "75% of the time, you can expect the patient to agree with you on their disease activity level. They are going to report a pretty similar score. But for the other 25% of the time, the patient’s going to say, ‘My disease is worse than what you think it is,’ " explained presenting author May Choi, a second-year medical student at the University of Alberta, Edmonton.

"We think it’s more a reflection of their subjective pain, and that pain is probably not in their joints – it probably has something to do with soft tissue pain, like fibromyalgia," she added. In patients with established disease, the pain appears to reflect "all of the joint damage they have accumulated over the years because of the RA. So it’s not a reflection of their current disease activity, but the damage that has resulted."

Physicians who find a discrepancy between assessments for a given patient should take a closer look to determine the reason, especially as it has implications for treatment, Ms. Choi advised in an interview. "If a patient is in a lot of pain, but a physician is feeling their joints and they don’t really see [an explanation for] what’s going on, they are not going to give them a drug for their joints. They are going to look at other reasons and treat them for that – pain that’s related to their soft tissues," she explained.

The study’s findings also suggest that the two assessments are complementary, and both should be used, she maintained. "I don’t think one is more important than the other. They provide different information" and in clinical studies, "absolutely, they should get both numbers to get the big picture."

Previous research has found a difference between physician and patient global assessments of RA disease activity, but the reason remains unknown, according to Ms. Choi. "This is an important question because physicians use this tool to monitor their patients, and we think it’s important to increase awareness that there is a difference. We wanted to look at reasons why this difference exists and what are its implications for patient management," she said.

For the study, which was supported by the Canadian Rheumatology Association–Roche Summer Studentship, the researchers identified 897 patients with early RA (mean disease duration, 0.5 years) from the Canadian Early Arthritis Cohort database and 100 patients with established RA in remission from one practice (mean disease duration, 18 years).

Scores were compared from the patient-completed PtGA and physician-completed MDGA. Discrepancy between results on the two 100-mm scales was assessed by subtracting the latter from the former and was classified as clinically meaningful if it was at least 30 mm.

Study results, reported in a poster session, revealed that in the early RA group, the PtGA and MDGA scores showed no discrepancy in 64% of patients. But in 24%, patients reported worse disease than their physicians did, and in 12%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting disease activity had lower swollen and tender joint counts and similar C-reactive protein levels. Yet they also reported more pain. "So here is a group of patients who are reporting a lot of pain, but it’s not in their joints necessarily," commented Ms. Choi. On the other hand, compared with their counterparts having no discrepancy, patients underreporting disease activity had higher swollen joint counts and C-reactive protein levels, and yet less pain. This finding may be related to differing pain thresholds across individuals, she noted, saying, "There are some patients like that. They are just not as sensitive."

In the established RA group, the PtGA and MDGA scores showed no discrepancy in 75% of patients. But in 24%, patients reported worse disease than their physicians did, and in 1%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting or under-reporting disease activity were younger; had a higher damaged joint count, erythrocyte sedimentation rate, and C-reactive protein level; and reported more pain.

"So in both groups, pain is a common theme," Ms. Choi pointed out. And indeed, additional analysis showed that reported pain scores were positively correlated with the magnitude of the PtGA-MDGA discrepancy (r = 0.84). Also, among the patients with established disease, pain scores were positively correlated with the number of damaged joints (rS = 0.37).

Ms. Choi said she had no relevant financial disclosures.

VICTORIA, B.C. – Physician and patient assessments of disease activity in rheumatoid arthritis show considerable disagreement that seems to be driven by subjective perceptions of pain, a study has shown.

The study involved nearly 900 patients with early rheumatoid arthritis (RA) and 100 patients with established RA in remission, all of whom had been treated only with disease-modifying antirheumatic drugs (DMARDs). Findings on physician and patient assessments of disease activity disagreed to a clinically meaningful extent roughly one-fourth to one-third of the time, based on the results of this as-yet unpublished study, reported at the annual meeting of the Canadian Rheumatology Association.

In most cases of discordance, patients rated their RA as being worse than their physicians did. Findings from additional analyses suggested that the discrepancy was largely due to subjective pain, and pain levels showed some association with cumulative RA-related joint damage.

"For a rheumatologist who is using these global assessment scores" – the patient global assessment (PtGA) and the physician global assessment (MDGA) – "75% of the time, you can expect the patient to agree with you on their disease activity level. They are going to report a pretty similar score. But for the other 25% of the time, the patient’s going to say, ‘My disease is worse than what you think it is,’ " explained presenting author May Choi, a second-year medical student at the University of Alberta, Edmonton.

"We think it’s more a reflection of their subjective pain, and that pain is probably not in their joints – it probably has something to do with soft tissue pain, like fibromyalgia," she added. In patients with established disease, the pain appears to reflect "all of the joint damage they have accumulated over the years because of the RA. So it’s not a reflection of their current disease activity, but the damage that has resulted."

Physicians who find a discrepancy between assessments for a given patient should take a closer look to determine the reason, especially as it has implications for treatment, Ms. Choi advised in an interview. "If a patient is in a lot of pain, but a physician is feeling their joints and they don’t really see [an explanation for] what’s going on, they are not going to give them a drug for their joints. They are going to look at other reasons and treat them for that – pain that’s related to their soft tissues," she explained.

The study’s findings also suggest that the two assessments are complementary, and both should be used, she maintained. "I don’t think one is more important than the other. They provide different information" and in clinical studies, "absolutely, they should get both numbers to get the big picture."

Previous research has found a difference between physician and patient global assessments of RA disease activity, but the reason remains unknown, according to Ms. Choi. "This is an important question because physicians use this tool to monitor their patients, and we think it’s important to increase awareness that there is a difference. We wanted to look at reasons why this difference exists and what are its implications for patient management," she said.

For the study, which was supported by the Canadian Rheumatology Association–Roche Summer Studentship, the researchers identified 897 patients with early RA (mean disease duration, 0.5 years) from the Canadian Early Arthritis Cohort database and 100 patients with established RA in remission from one practice (mean disease duration, 18 years).

Scores were compared from the patient-completed PtGA and physician-completed MDGA. Discrepancy between results on the two 100-mm scales was assessed by subtracting the latter from the former and was classified as clinically meaningful if it was at least 30 mm.

Study results, reported in a poster session, revealed that in the early RA group, the PtGA and MDGA scores showed no discrepancy in 64% of patients. But in 24%, patients reported worse disease than their physicians did, and in 12%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting disease activity had lower swollen and tender joint counts and similar C-reactive protein levels. Yet they also reported more pain. "So here is a group of patients who are reporting a lot of pain, but it’s not in their joints necessarily," commented Ms. Choi. On the other hand, compared with their counterparts having no discrepancy, patients underreporting disease activity had higher swollen joint counts and C-reactive protein levels, and yet less pain. This finding may be related to differing pain thresholds across individuals, she noted, saying, "There are some patients like that. They are just not as sensitive."

In the established RA group, the PtGA and MDGA scores showed no discrepancy in 75% of patients. But in 24%, patients reported worse disease than their physicians did, and in 1%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting or under-reporting disease activity were younger; had a higher damaged joint count, erythrocyte sedimentation rate, and C-reactive protein level; and reported more pain.

"So in both groups, pain is a common theme," Ms. Choi pointed out. And indeed, additional analysis showed that reported pain scores were positively correlated with the magnitude of the PtGA-MDGA discrepancy (r = 0.84). Also, among the patients with established disease, pain scores were positively correlated with the number of damaged joints (rS = 0.37).

Ms. Choi said she had no relevant financial disclosures.

VICTORIA, B.C. – Physician and patient assessments of disease activity in rheumatoid arthritis show considerable disagreement that seems to be driven by subjective perceptions of pain, a study has shown.

The study involved nearly 900 patients with early rheumatoid arthritis (RA) and 100 patients with established RA in remission, all of whom had been treated only with disease-modifying antirheumatic drugs (DMARDs). Findings on physician and patient assessments of disease activity disagreed to a clinically meaningful extent roughly one-fourth to one-third of the time, based on the results of this as-yet unpublished study, reported at the annual meeting of the Canadian Rheumatology Association.

In most cases of discordance, patients rated their RA as being worse than their physicians did. Findings from additional analyses suggested that the discrepancy was largely due to subjective pain, and pain levels showed some association with cumulative RA-related joint damage.

"For a rheumatologist who is using these global assessment scores" – the patient global assessment (PtGA) and the physician global assessment (MDGA) – "75% of the time, you can expect the patient to agree with you on their disease activity level. They are going to report a pretty similar score. But for the other 25% of the time, the patient’s going to say, ‘My disease is worse than what you think it is,’ " explained presenting author May Choi, a second-year medical student at the University of Alberta, Edmonton.

"We think it’s more a reflection of their subjective pain, and that pain is probably not in their joints – it probably has something to do with soft tissue pain, like fibromyalgia," she added. In patients with established disease, the pain appears to reflect "all of the joint damage they have accumulated over the years because of the RA. So it’s not a reflection of their current disease activity, but the damage that has resulted."

Physicians who find a discrepancy between assessments for a given patient should take a closer look to determine the reason, especially as it has implications for treatment, Ms. Choi advised in an interview. "If a patient is in a lot of pain, but a physician is feeling their joints and they don’t really see [an explanation for] what’s going on, they are not going to give them a drug for their joints. They are going to look at other reasons and treat them for that – pain that’s related to their soft tissues," she explained.

The study’s findings also suggest that the two assessments are complementary, and both should be used, she maintained. "I don’t think one is more important than the other. They provide different information" and in clinical studies, "absolutely, they should get both numbers to get the big picture."

Previous research has found a difference between physician and patient global assessments of RA disease activity, but the reason remains unknown, according to Ms. Choi. "This is an important question because physicians use this tool to monitor their patients, and we think it’s important to increase awareness that there is a difference. We wanted to look at reasons why this difference exists and what are its implications for patient management," she said.

For the study, which was supported by the Canadian Rheumatology Association–Roche Summer Studentship, the researchers identified 897 patients with early RA (mean disease duration, 0.5 years) from the Canadian Early Arthritis Cohort database and 100 patients with established RA in remission from one practice (mean disease duration, 18 years).

Scores were compared from the patient-completed PtGA and physician-completed MDGA. Discrepancy between results on the two 100-mm scales was assessed by subtracting the latter from the former and was classified as clinically meaningful if it was at least 30 mm.

Study results, reported in a poster session, revealed that in the early RA group, the PtGA and MDGA scores showed no discrepancy in 64% of patients. But in 24%, patients reported worse disease than their physicians did, and in 12%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting disease activity had lower swollen and tender joint counts and similar C-reactive protein levels. Yet they also reported more pain. "So here is a group of patients who are reporting a lot of pain, but it’s not in their joints necessarily," commented Ms. Choi. On the other hand, compared with their counterparts having no discrepancy, patients underreporting disease activity had higher swollen joint counts and C-reactive protein levels, and yet less pain. This finding may be related to differing pain thresholds across individuals, she noted, saying, "There are some patients like that. They are just not as sensitive."

In the established RA group, the PtGA and MDGA scores showed no discrepancy in 75% of patients. But in 24%, patients reported worse disease than their physicians did, and in 1%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting or under-reporting disease activity were younger; had a higher damaged joint count, erythrocyte sedimentation rate, and C-reactive protein level; and reported more pain.

"So in both groups, pain is a common theme," Ms. Choi pointed out. And indeed, additional analysis showed that reported pain scores were positively correlated with the magnitude of the PtGA-MDGA discrepancy (r = 0.84). Also, among the patients with established disease, pain scores were positively correlated with the number of damaged joints (rS = 0.37).

Ms. Choi said she had no relevant financial disclosures.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

VICTORIA, B.C. – Autoantibodies directed against homocitrullinated fibrinogen may help identify patients with rheumatoid arthritis who would currently be missed, a study has shown.

A team led by Dr. Lillian Barra and Dr. Ewa Cairns of the University of Western Ontario, London, tested 84 patients with rheumatoid arthritis (RA) and found that nearly half had antihomocitrullinated fibrinogen antibodies (AHFAs) in their serum.

Perhaps most importantly, these antibodies were present in almost a fifth of patients who did not have anticitrullinated fibrinogen antibodies (ACFAs) and would thus have otherwise been considered to be seronegative.

The results also indicated that AHFAs were specific for RA: They were seldom found in 37 patients with systemic lupus erythematosus and 37 patients with psoriatic arthritis. And they were not found at all in any of 27 healthy volunteers.

These findings add to similar results seen in a cohort of patients from Leiden, the Netherlands (Proc. Natl. Acad. Sci. USA 2011;108:17372-7), noted Dr. Barra, who presented the findings at the annual meeting of the Canadian Rheumatology Association "This is an exploratory study, and we are going to do a lot of future work looking at these antibodies in a larger cohort, hopefully the CATCH [Canadian Arthritis Cohort]," she said.

The large collective group of anticitrullinated protein antibodies (ACPAs) target citrullinated proteins, such as the collagen, fibrinogen, and vimentin found in joint synovial fluid. "They are highly specific for rheumatoid arthritis and have been included in the new [American College of Rheumatology]-EULAR criteria" for diagnosing early disease, Dr. Barra pointed out.

ACPAs associate with the shared epitope, the strongest genetic risk factor for RA, and have been found to be pathogenic in mice, she further noted. "However, nearly 50% of patients with early rheumatoid arthritis do not have ACPAs, which begs the question of whether these patients have a different type of antibody that we don’t know about."

The investigators recruited patients meeting diagnostic criteria for various rheumatologic diseases from St. Joseph’s Health Care in Southwestern Ontario, nearly all of whom were white. They also recruited age- and sex-matched healthy volunteers.

Descriptive data indicated that, on average, the patients with rheumatoid arthritis had had their disease for about 9 years and had 4.3 swollen joints, Dr. Barra reported. Fifty-six percent were in remission.

The main study results showed that 49% of patients with rheumatoid arthritis overall had AHFAs. This compared with just 5% of patients with SLE, 3% of patients with psoriatic arthritis, and none of the healthy volunteers.

A full 31% of the patients with RA were negative for ACFAs, but 19% of this subgroup were found to have AHFAs. Viewed another way, 6% of the patients with RA overall were negative for ACFAs but positive for AHFAs. "These patients were previously considered seronegative, but they do have an antibody," Dr. Barra commented.

The investigators also used a computer algorithm to assess whether the proteins and peptides that are homocitrullinated would bind to the shared epitope. The results indicated that 35 of them, only 5 of which could also be citrullinated, would bind with high affinity. "This suggests that there are unique homocitrullinated peptides, but there is also the possibility of cross-reactivity" between AHFAs and ACFAs, she explained.

"We are going to investigate cross-reactivity further, and we would like to look at the immune responses [to these proteins] in vivo in future work," Dr. Barra concluded.

Dr. Barra said she had no relevant financial disclosures.

VICTORIA, B.C. – Autoantibodies directed against homocitrullinated fibrinogen may help identify patients with rheumatoid arthritis who would currently be missed, a study has shown.

A team led by Dr. Lillian Barra and Dr. Ewa Cairns of the University of Western Ontario, London, tested 84 patients with rheumatoid arthritis (RA) and found that nearly half had antihomocitrullinated fibrinogen antibodies (AHFAs) in their serum.

Perhaps most importantly, these antibodies were present in almost a fifth of patients who did not have anticitrullinated fibrinogen antibodies (ACFAs) and would thus have otherwise been considered to be seronegative.

The results also indicated that AHFAs were specific for RA: They were seldom found in 37 patients with systemic lupus erythematosus and 37 patients with psoriatic arthritis. And they were not found at all in any of 27 healthy volunteers.

These findings add to similar results seen in a cohort of patients from Leiden, the Netherlands (Proc. Natl. Acad. Sci. USA 2011;108:17372-7), noted Dr. Barra, who presented the findings at the annual meeting of the Canadian Rheumatology Association "This is an exploratory study, and we are going to do a lot of future work looking at these antibodies in a larger cohort, hopefully the CATCH [Canadian Arthritis Cohort]," she said.

The large collective group of anticitrullinated protein antibodies (ACPAs) target citrullinated proteins, such as the collagen, fibrinogen, and vimentin found in joint synovial fluid. "They are highly specific for rheumatoid arthritis and have been included in the new [American College of Rheumatology]-EULAR criteria" for diagnosing early disease, Dr. Barra pointed out.

ACPAs associate with the shared epitope, the strongest genetic risk factor for RA, and have been found to be pathogenic in mice, she further noted. "However, nearly 50% of patients with early rheumatoid arthritis do not have ACPAs, which begs the question of whether these patients have a different type of antibody that we don’t know about."

The investigators recruited patients meeting diagnostic criteria for various rheumatologic diseases from St. Joseph’s Health Care in Southwestern Ontario, nearly all of whom were white. They also recruited age- and sex-matched healthy volunteers.

Descriptive data indicated that, on average, the patients with rheumatoid arthritis had had their disease for about 9 years and had 4.3 swollen joints, Dr. Barra reported. Fifty-six percent were in remission.

The main study results showed that 49% of patients with rheumatoid arthritis overall had AHFAs. This compared with just 5% of patients with SLE, 3% of patients with psoriatic arthritis, and none of the healthy volunteers.

A full 31% of the patients with RA were negative for ACFAs, but 19% of this subgroup were found to have AHFAs. Viewed another way, 6% of the patients with RA overall were negative for ACFAs but positive for AHFAs. "These patients were previously considered seronegative, but they do have an antibody," Dr. Barra commented.

The investigators also used a computer algorithm to assess whether the proteins and peptides that are homocitrullinated would bind to the shared epitope. The results indicated that 35 of them, only 5 of which could also be citrullinated, would bind with high affinity. "This suggests that there are unique homocitrullinated peptides, but there is also the possibility of cross-reactivity" between AHFAs and ACFAs, she explained.

"We are going to investigate cross-reactivity further, and we would like to look at the immune responses [to these proteins] in vivo in future work," Dr. Barra concluded.

Dr. Barra said she had no relevant financial disclosures.

VICTORIA, B.C. – Autoantibodies directed against homocitrullinated fibrinogen may help identify patients with rheumatoid arthritis who would currently be missed, a study has shown.

A team led by Dr. Lillian Barra and Dr. Ewa Cairns of the University of Western Ontario, London, tested 84 patients with rheumatoid arthritis (RA) and found that nearly half had antihomocitrullinated fibrinogen antibodies (AHFAs) in their serum.

Perhaps most importantly, these antibodies were present in almost a fifth of patients who did not have anticitrullinated fibrinogen antibodies (ACFAs) and would thus have otherwise been considered to be seronegative.

The results also indicated that AHFAs were specific for RA: They were seldom found in 37 patients with systemic lupus erythematosus and 37 patients with psoriatic arthritis. And they were not found at all in any of 27 healthy volunteers.

These findings add to similar results seen in a cohort of patients from Leiden, the Netherlands (Proc. Natl. Acad. Sci. USA 2011;108:17372-7), noted Dr. Barra, who presented the findings at the annual meeting of the Canadian Rheumatology Association "This is an exploratory study, and we are going to do a lot of future work looking at these antibodies in a larger cohort, hopefully the CATCH [Canadian Arthritis Cohort]," she said.

The large collective group of anticitrullinated protein antibodies (ACPAs) target citrullinated proteins, such as the collagen, fibrinogen, and vimentin found in joint synovial fluid. "They are highly specific for rheumatoid arthritis and have been included in the new [American College of Rheumatology]-EULAR criteria" for diagnosing early disease, Dr. Barra pointed out.

ACPAs associate with the shared epitope, the strongest genetic risk factor for RA, and have been found to be pathogenic in mice, she further noted. "However, nearly 50% of patients with early rheumatoid arthritis do not have ACPAs, which begs the question of whether these patients have a different type of antibody that we don’t know about."

The investigators recruited patients meeting diagnostic criteria for various rheumatologic diseases from St. Joseph’s Health Care in Southwestern Ontario, nearly all of whom were white. They also recruited age- and sex-matched healthy volunteers.

Descriptive data indicated that, on average, the patients with rheumatoid arthritis had had their disease for about 9 years and had 4.3 swollen joints, Dr. Barra reported. Fifty-six percent were in remission.

The main study results showed that 49% of patients with rheumatoid arthritis overall had AHFAs. This compared with just 5% of patients with SLE, 3% of patients with psoriatic arthritis, and none of the healthy volunteers.

A full 31% of the patients with RA were negative for ACFAs, but 19% of this subgroup were found to have AHFAs. Viewed another way, 6% of the patients with RA overall were negative for ACFAs but positive for AHFAs. "These patients were previously considered seronegative, but they do have an antibody," Dr. Barra commented.

The investigators also used a computer algorithm to assess whether the proteins and peptides that are homocitrullinated would bind to the shared epitope. The results indicated that 35 of them, only 5 of which could also be citrullinated, would bind with high affinity. "This suggests that there are unique homocitrullinated peptides, but there is also the possibility of cross-reactivity" between AHFAs and ACFAs, she explained.

"We are going to investigate cross-reactivity further, and we would like to look at the immune responses [to these proteins] in vivo in future work," Dr. Barra concluded.

Dr. Barra said she had no relevant financial disclosures.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW ORLEANS – Physicians are feeling the heat over the highly publicized national public health crisis stemming from overprescribing oxycodone for non-cancer chronic pain. One result has been a huge shift to using methadone for that indication. But is that the answer?

Methadone is widely perceived as an attractive alternative to oxycodone because it’s less euphoria-inducing and thus somewhat less prone to abuse, as well as less expensive. But the reality is it’s a very tricky drug to use safely for pain management, according to Dr. Barak Gaster, a general internist at the University of Washington, Seattle.

Methadone is a highly unusual opiate. The dose-response relationship is far more variable and idiosyncratic than for oxycodone or other opiates. Methadone has numerous active metabolites. And as those active metabolites accumulate during the first 2 weeks on any given dose of the drug, patients will gradually experience greater analgesia and, disturbingly, more respiratory depression as well.

"This is one of the most dangerous situations for unintentional overdose. Patients have to understand that this is kind of a dangerous medication, and it’s going to take a couple weeks to kick in during which it’s absolutely essential that they don’t increase the dose on their own," Dr. Gaster explained at the annual meeting of the American College of Physicians.

The other major shortcoming of methadone as a treatment for chronic pain is that the drug comes in big-dose tablets designed for once-daily treatment of heroin addiction. The smallest available dose – a 5-mg tablet – is 3-4 times more potent than a 5-mg pill of oxycodone. So patients placed on 5 mg per day of methadone are really being started at 3 times the usual starting dose of oxycodone, hydrocodone, or morphine. And 60 mg of methadone is really more like 200 mg of oxycodone.

An opiate-naive individual should be started on half a 5-mg tablet of methadone twice daily for 2 weeks. Titration should then proceed very slowly, since it takes about 2 weeks for each new dose to reach steady state.

"There’s a weird Catch-22 situation with methadone where on the one hand it’s a short-acting drug in terms of its analgesic effect and needs to be dosed at least 3 times a day, but on the other hand it has this very long-acting risk potential," the internist observed.

The burgeoning shift from away from prescribing oxycodone in favor of methadone for chronic pain is fueled by a general recognition that something has gone very much awry nationally with regard to opiate prescribing. Prescriptions for opiates have tripled in the last 10 years. Surveys indicate 1 in 20 American adults has taken prescription opiates to get high. Most disturbingly, the annual number of unintentional fatal overdoses attributed to prescription opiates now exceeds those from heroin and cocaine combined.

Of note, Dr. Gaster observed, these unintentional fatal opiate overdoses very rarely occur in individuals who are on a single somnolence-inducing medication. The classic setup is the patient who is on an opioid for chronic pain, but who is also drinking alcohol, taking a benzodiazepine, and has sleep apnea.

He reported having no financial conflicts.

NEW ORLEANS – Physicians are feeling the heat over the highly publicized national public health crisis stemming from overprescribing oxycodone for non-cancer chronic pain. One result has been a huge shift to using methadone for that indication. But is that the answer?

Methadone is widely perceived as an attractive alternative to oxycodone because it’s less euphoria-inducing and thus somewhat less prone to abuse, as well as less expensive. But the reality is it’s a very tricky drug to use safely for pain management, according to Dr. Barak Gaster, a general internist at the University of Washington, Seattle.

Methadone is a highly unusual opiate. The dose-response relationship is far more variable and idiosyncratic than for oxycodone or other opiates. Methadone has numerous active metabolites. And as those active metabolites accumulate during the first 2 weeks on any given dose of the drug, patients will gradually experience greater analgesia and, disturbingly, more respiratory depression as well.

"This is one of the most dangerous situations for unintentional overdose. Patients have to understand that this is kind of a dangerous medication, and it’s going to take a couple weeks to kick in during which it’s absolutely essential that they don’t increase the dose on their own," Dr. Gaster explained at the annual meeting of the American College of Physicians.

The other major shortcoming of methadone as a treatment for chronic pain is that the drug comes in big-dose tablets designed for once-daily treatment of heroin addiction. The smallest available dose – a 5-mg tablet – is 3-4 times more potent than a 5-mg pill of oxycodone. So patients placed on 5 mg per day of methadone are really being started at 3 times the usual starting dose of oxycodone, hydrocodone, or morphine. And 60 mg of methadone is really more like 200 mg of oxycodone.

An opiate-naive individual should be started on half a 5-mg tablet of methadone twice daily for 2 weeks. Titration should then proceed very slowly, since it takes about 2 weeks for each new dose to reach steady state.

"There’s a weird Catch-22 situation with methadone where on the one hand it’s a short-acting drug in terms of its analgesic effect and needs to be dosed at least 3 times a day, but on the other hand it has this very long-acting risk potential," the internist observed.

The burgeoning shift from away from prescribing oxycodone in favor of methadone for chronic pain is fueled by a general recognition that something has gone very much awry nationally with regard to opiate prescribing. Prescriptions for opiates have tripled in the last 10 years. Surveys indicate 1 in 20 American adults has taken prescription opiates to get high. Most disturbingly, the annual number of unintentional fatal overdoses attributed to prescription opiates now exceeds those from heroin and cocaine combined.

Of note, Dr. Gaster observed, these unintentional fatal opiate overdoses very rarely occur in individuals who are on a single somnolence-inducing medication. The classic setup is the patient who is on an opioid for chronic pain, but who is also drinking alcohol, taking a benzodiazepine, and has sleep apnea.

He reported having no financial conflicts.

NEW ORLEANS – Physicians are feeling the heat over the highly publicized national public health crisis stemming from overprescribing oxycodone for non-cancer chronic pain. One result has been a huge shift to using methadone for that indication. But is that the answer?

Methadone is widely perceived as an attractive alternative to oxycodone because it’s less euphoria-inducing and thus somewhat less prone to abuse, as well as less expensive. But the reality is it’s a very tricky drug to use safely for pain management, according to Dr. Barak Gaster, a general internist at the University of Washington, Seattle.

Methadone is a highly unusual opiate. The dose-response relationship is far more variable and idiosyncratic than for oxycodone or other opiates. Methadone has numerous active metabolites. And as those active metabolites accumulate during the first 2 weeks on any given dose of the drug, patients will gradually experience greater analgesia and, disturbingly, more respiratory depression as well.

"This is one of the most dangerous situations for unintentional overdose. Patients have to understand that this is kind of a dangerous medication, and it’s going to take a couple weeks to kick in during which it’s absolutely essential that they don’t increase the dose on their own," Dr. Gaster explained at the annual meeting of the American College of Physicians.

The other major shortcoming of methadone as a treatment for chronic pain is that the drug comes in big-dose tablets designed for once-daily treatment of heroin addiction. The smallest available dose – a 5-mg tablet – is 3-4 times more potent than a 5-mg pill of oxycodone. So patients placed on 5 mg per day of methadone are really being started at 3 times the usual starting dose of oxycodone, hydrocodone, or morphine. And 60 mg of methadone is really more like 200 mg of oxycodone.

An opiate-naive individual should be started on half a 5-mg tablet of methadone twice daily for 2 weeks. Titration should then proceed very slowly, since it takes about 2 weeks for each new dose to reach steady state.

"There’s a weird Catch-22 situation with methadone where on the one hand it’s a short-acting drug in terms of its analgesic effect and needs to be dosed at least 3 times a day, but on the other hand it has this very long-acting risk potential," the internist observed.

The burgeoning shift from away from prescribing oxycodone in favor of methadone for chronic pain is fueled by a general recognition that something has gone very much awry nationally with regard to opiate prescribing. Prescriptions for opiates have tripled in the last 10 years. Surveys indicate 1 in 20 American adults has taken prescription opiates to get high. Most disturbingly, the annual number of unintentional fatal overdoses attributed to prescription opiates now exceeds those from heroin and cocaine combined.

Of note, Dr. Gaster observed, these unintentional fatal opiate overdoses very rarely occur in individuals who are on a single somnolence-inducing medication. The classic setup is the patient who is on an opioid for chronic pain, but who is also drinking alcohol, taking a benzodiazepine, and has sleep apnea.

He reported having no financial conflicts.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.