Rheumatoid Arthritis

Major Finding: After investigators controlled for age and sex, Spearman's correlation coefficients showed a significant relationship between all measures of physical functioning and CRP level in early RA, but no correlation between those measures and modified Total Sharp Score (mTSS). In longstanding RA, the measures of physical functioning were significantly correlated with mTSS and with CRP.

Data Source: From a pooled analysis of data from two trials of RA patients.

Disclosures: Dr. Bergman disclosed that he has received research grants and consulting fees or other remuneration, and/or served on the speakers bureau for Abbott Laboratories, Bristol-Meyers Squibb, Roche, and UCB.

ATLANTA — Physical functioning in rheumatoid arthritis patients is affected more by inflammation early in the disease process, and more by structural damage as the disease progresses, according to an analysis of pooled data from two large clinical trials.

“We feel that this study confirms that deterioration of physical functioning as a result of RA may be driven predominantly by inflammation earlier in the course of disease, but over time it is driven more by structural damage than it is by inflammation. It also suggests that earlier treatment of these patients with appropriate therapy prior to development of significant structural damage should dramatically improve the long-term physical function and disability outcomes of our patients with rheumatoid arthritis,” reported Dr. Martin J. Bergman.

Dr. Bergman and his colleagues studied 1,415 patients from the two trials, each of which assessed the effects of adalimumab in RA: The PREMIER (Prospective Registry Evaluating Outcomes After Myocardial Infarction: Events and Recovery) trial was a double-blind, placebo-controlled phase III trial in patients with early RA, and the DE019 trial was a randomized, placebo-controlled trial of patients with established RA. A total of 908 patients from these trials had a disease duration of 3 years or less, and 507 had a disease duration of greater than 3 years.

“We pooled data to assess the relationship between structural damage as measured by the modified Total Sharp Score, joint space narrowing, and joint erosions. We also looked at inflammation as measured by C-reactive protein,” said Dr. Bergman, who is both on the staff of the division of rheumatology at Drexel University in Philadelphia, and chief of the division of rheumatology at Taylor Hospital of Arthritis and Rheumatology in Ridley Park, Pa.

Physical functioning was assessed using the Health Assessment Questionnaire (HAQ), and the Physical Component Score and Physical Functioning domain of the Short Form (SF)-36 Questionnaire, which assesses quality of life, he said.

Spearman's correlation coefficients showed a significant relationship between all three measures of physical function and C-reactive protein in early RA, but no correlation between those measures and a modified Total Sharp Score (mTSS).

In patients with longstanding RA, the measures of function were significantly correlated with mTSS and with CRP – although the latter associations were weaker than those seen in early disease, Dr. Bergman concluded.

Major Finding: After investigators controlled for age and sex, Spearman's correlation coefficients showed a significant relationship between all measures of physical functioning and CRP level in early RA, but no correlation between those measures and modified Total Sharp Score (mTSS). In longstanding RA, the measures of physical functioning were significantly correlated with mTSS and with CRP.

Data Source: From a pooled analysis of data from two trials of RA patients.

Disclosures: Dr. Bergman disclosed that he has received research grants and consulting fees or other remuneration, and/or served on the speakers bureau for Abbott Laboratories, Bristol-Meyers Squibb, Roche, and UCB.

ATLANTA — Physical functioning in rheumatoid arthritis patients is affected more by inflammation early in the disease process, and more by structural damage as the disease progresses, according to an analysis of pooled data from two large clinical trials.

“We feel that this study confirms that deterioration of physical functioning as a result of RA may be driven predominantly by inflammation earlier in the course of disease, but over time it is driven more by structural damage than it is by inflammation. It also suggests that earlier treatment of these patients with appropriate therapy prior to development of significant structural damage should dramatically improve the long-term physical function and disability outcomes of our patients with rheumatoid arthritis,” reported Dr. Martin J. Bergman.

Dr. Bergman and his colleagues studied 1,415 patients from the two trials, each of which assessed the effects of adalimumab in RA: The PREMIER (Prospective Registry Evaluating Outcomes After Myocardial Infarction: Events and Recovery) trial was a double-blind, placebo-controlled phase III trial in patients with early RA, and the DE019 trial was a randomized, placebo-controlled trial of patients with established RA. A total of 908 patients from these trials had a disease duration of 3 years or less, and 507 had a disease duration of greater than 3 years.

“We pooled data to assess the relationship between structural damage as measured by the modified Total Sharp Score, joint space narrowing, and joint erosions. We also looked at inflammation as measured by C-reactive protein,” said Dr. Bergman, who is both on the staff of the division of rheumatology at Drexel University in Philadelphia, and chief of the division of rheumatology at Taylor Hospital of Arthritis and Rheumatology in Ridley Park, Pa.

Physical functioning was assessed using the Health Assessment Questionnaire (HAQ), and the Physical Component Score and Physical Functioning domain of the Short Form (SF)-36 Questionnaire, which assesses quality of life, he said.

Spearman's correlation coefficients showed a significant relationship between all three measures of physical function and C-reactive protein in early RA, but no correlation between those measures and a modified Total Sharp Score (mTSS).

In patients with longstanding RA, the measures of function were significantly correlated with mTSS and with CRP – although the latter associations were weaker than those seen in early disease, Dr. Bergman concluded.

Major Finding: After investigators controlled for age and sex, Spearman's correlation coefficients showed a significant relationship between all measures of physical functioning and CRP level in early RA, but no correlation between those measures and modified Total Sharp Score (mTSS). In longstanding RA, the measures of physical functioning were significantly correlated with mTSS and with CRP.

Data Source: From a pooled analysis of data from two trials of RA patients.

Disclosures: Dr. Bergman disclosed that he has received research grants and consulting fees or other remuneration, and/or served on the speakers bureau for Abbott Laboratories, Bristol-Meyers Squibb, Roche, and UCB.

ATLANTA — Physical functioning in rheumatoid arthritis patients is affected more by inflammation early in the disease process, and more by structural damage as the disease progresses, according to an analysis of pooled data from two large clinical trials.

“We feel that this study confirms that deterioration of physical functioning as a result of RA may be driven predominantly by inflammation earlier in the course of disease, but over time it is driven more by structural damage than it is by inflammation. It also suggests that earlier treatment of these patients with appropriate therapy prior to development of significant structural damage should dramatically improve the long-term physical function and disability outcomes of our patients with rheumatoid arthritis,” reported Dr. Martin J. Bergman.

Dr. Bergman and his colleagues studied 1,415 patients from the two trials, each of which assessed the effects of adalimumab in RA: The PREMIER (Prospective Registry Evaluating Outcomes After Myocardial Infarction: Events and Recovery) trial was a double-blind, placebo-controlled phase III trial in patients with early RA, and the DE019 trial was a randomized, placebo-controlled trial of patients with established RA. A total of 908 patients from these trials had a disease duration of 3 years or less, and 507 had a disease duration of greater than 3 years.

“We pooled data to assess the relationship between structural damage as measured by the modified Total Sharp Score, joint space narrowing, and joint erosions. We also looked at inflammation as measured by C-reactive protein,” said Dr. Bergman, who is both on the staff of the division of rheumatology at Drexel University in Philadelphia, and chief of the division of rheumatology at Taylor Hospital of Arthritis and Rheumatology in Ridley Park, Pa.

Physical functioning was assessed using the Health Assessment Questionnaire (HAQ), and the Physical Component Score and Physical Functioning domain of the Short Form (SF)-36 Questionnaire, which assesses quality of life, he said.

Spearman's correlation coefficients showed a significant relationship between all three measures of physical function and C-reactive protein in early RA, but no correlation between those measures and a modified Total Sharp Score (mTSS).

In patients with longstanding RA, the measures of function were significantly correlated with mTSS and with CRP – although the latter associations were weaker than those seen in early disease, Dr. Bergman concluded.

Major Finding: Each of seven NSAIDs was associated with significantly increased risk for MI, stroke, or death from cardiovascular disease, compared with placebo.

Data Source: Network meta-analysis of 31 large, randomized controlled trials comparing any NSAID with other NSAIDs or placebo in 116,429 patients with 117,218 patient-years of follow-up.

Disclosures: The Swiss National Science Foundation funded the study. The investigators reported having no conflicts of interest.

Each of seven NSAIDs was associated with significantly increased risk for MI, stroke, or death from cardiovascular disease, compared with placebo, in the most comprehensive meta-analysis of the subject so far.

The relative risks with any individual NSAID, compared with placebo, often were double, triple, or quadruple the risk with placebo, the study found. The absolute numbers of MIs and other cardiovascular outcomes were small, but the network meta-analysis design of the study “provides the best available evidence on the safety of this class of drugs,” Dr. Sven Trelle and his associates reported.

Contrary to some previous reports, the current study also found no suggestion that this increased cardiovascular risk is specific to cyclo-oxygenase-2 (COX-2) inhibitors. Therefore the use of all NSAIDs – and the over-the-counter availability of some of them – should be reconsidered, Dr. Trelle stated in a report published online by BMJ (Jan. 11, 2011;342:c7086[doi/10.1136/bmj.c7086]).

Dr. Trelle of the University of Bern, Switzerland, acknowledged that therapeutic options for chronic musculoskeletal pain are limited, but cautioned that “cardiovascular risk needs to be taken into account when prescribing” any NSAID.

The meta-analysis included any large, randomized controlled trials comparing any NSAID with other NSAIDs or placebo. Data were available for naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, and lumiracoxib. The risk for a cardiovascular event had to increase by more than 30% to be considered significant.

Overall, naproxen appeared to be the least harmful NSAID in terms of cardiovascular outcomes. Risks were greatest with ibuprofen, diclofenac, etoricoxib, and lumiracoxib.

Four NSAIDs were associated with significantly increased risk for myocardial infarction (the primary outcome in the current analysis) in 29 of the trials that reported 554 MIs. The relative risk for MI doubled with rofecoxib or lumiracoxib, was 35% higher with celecoxib, and was 61% higher with ibuprofen, compared with placebo. Evidence was lacking for increased MI risk with the other three NSAIDs.

Among secondary outcomes, stroke risk increased with all NSAIDs in 26 trials that reported 377 strokes. The increased risk was significant with four of the drugs, roughly doubling with naproxen and tripling with ibuprofen, diclofenac, etoricoxib, or lumiracoxib, compared with placebo.

Twenty-six trials reported 312 deaths from cardiovascular disease, accounting for 46% of all deaths in the trials. All NSAIDs except naproxen were associated with higher risk for cardiovascular death, which increased by 58% with rofecoxib, roughly doubled with ibuprofen, celecoxib, or lumiracoxib, and increased approximately fourfold with diclofenac or etoricoxib, compared with placebo.

All the NSAIDs were associated with increased risk for death from any cause, compared with placebo, and the increase was significant for all except naproxen. There were 676 deaths from any cause in 28 trials, and the risk of death roughly doubled with any of the other six NSAIDs.

Looking at a composite of nonfatal MI, nonfatal stroke, or cardiovascular death in 30 trials that reported 1,091 composite events, the risk increased with all the NSAIDs and increased significantly with all but naproxen.

View on the News

Time to Reevaluate NSAIDs

The cardiotoxicity of NSAIDs is particularly worrisome because many patients have both cardiovascular disease and musculoskeletal disease, Wayne A. Ray, Ph.D., noted in an editorial accompanying Dr. Trelle's study (BMJ Jan. 11, 2011;342:c6618 [doi:10.1136/bmj. c6618]).

What Dr. Trelle's study adds to the existing literature on NSAIDs is the potentially powerful technique known as network meta-analysis, which can extract more information from the data when certain assumptions are met, compared with traditional analyses, he wrote. The strength of the technique is that it uses all of the data, but it has some inherent weaknesses that should inspire caution when interpreting estimates based on indirect comparisons, explained Dr. Ray.

For example, no large, placebo-controlled trials compared etoricoxib vs. placebo. Risks of etoricoxib vs. placebo were estimated based on a chain of direct comparisons in separate trials – etoricoxib vs. diclofenac; diclofenac vs. rofecoxib or celecoxib, and finally rofecoxib or celecoxib vs. placebo.

Based on all the studies, what are the best strategies for clinicians who are considering NSAIDs for patients at high risk of cardiovascular disease? Avoid COX-2 inhibitors, especially in higher doses, Dr. Ray advised. Avoid diclofenac. Remember that ibuprofen may attenuate the antiplatelet effects of aspirin.

For now, naproxen seems to be the safest NSAID in terms of cardiovascular risk.

With any NSAID, consider also prescribing gastroprotective drugs.

NSAIDs are not the only option for treatment of musculoskeletal symptoms. Clinicians also prescribe paracetamol, low-dose opioid analgesics, and newer drugs, but without large-scale comparison studies, it's impossible to tell which is best for both efficacy and safety, Dr. Ray wrote. “Perhaps it is time for a larger, more systematic evaluation of a broader range of alternatives,” he suggested.

DR. WAYNE A. RAY is a professor and director of pharmacoepidemiology at Vanderbilt University, Nashville, Tenn. Dr. Ray has received financial support from Pfizer, was a paid expert witness in a lawsuit by the state of Texas against Merck, and is a paid expert in an insurance company action against the maker of Prempro.

Major Finding: Each of seven NSAIDs was associated with significantly increased risk for MI, stroke, or death from cardiovascular disease, compared with placebo.

Data Source: Network meta-analysis of 31 large, randomized controlled trials comparing any NSAID with other NSAIDs or placebo in 116,429 patients with 117,218 patient-years of follow-up.

Disclosures: The Swiss National Science Foundation funded the study. The investigators reported having no conflicts of interest.

Each of seven NSAIDs was associated with significantly increased risk for MI, stroke, or death from cardiovascular disease, compared with placebo, in the most comprehensive meta-analysis of the subject so far.

The relative risks with any individual NSAID, compared with placebo, often were double, triple, or quadruple the risk with placebo, the study found. The absolute numbers of MIs and other cardiovascular outcomes were small, but the network meta-analysis design of the study “provides the best available evidence on the safety of this class of drugs,” Dr. Sven Trelle and his associates reported.

Contrary to some previous reports, the current study also found no suggestion that this increased cardiovascular risk is specific to cyclo-oxygenase-2 (COX-2) inhibitors. Therefore the use of all NSAIDs – and the over-the-counter availability of some of them – should be reconsidered, Dr. Trelle stated in a report published online by BMJ (Jan. 11, 2011;342:c7086[doi/10.1136/bmj.c7086]).

Dr. Trelle of the University of Bern, Switzerland, acknowledged that therapeutic options for chronic musculoskeletal pain are limited, but cautioned that “cardiovascular risk needs to be taken into account when prescribing” any NSAID.

The meta-analysis included any large, randomized controlled trials comparing any NSAID with other NSAIDs or placebo. Data were available for naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, and lumiracoxib. The risk for a cardiovascular event had to increase by more than 30% to be considered significant.

Overall, naproxen appeared to be the least harmful NSAID in terms of cardiovascular outcomes. Risks were greatest with ibuprofen, diclofenac, etoricoxib, and lumiracoxib.

Four NSAIDs were associated with significantly increased risk for myocardial infarction (the primary outcome in the current analysis) in 29 of the trials that reported 554 MIs. The relative risk for MI doubled with rofecoxib or lumiracoxib, was 35% higher with celecoxib, and was 61% higher with ibuprofen, compared with placebo. Evidence was lacking for increased MI risk with the other three NSAIDs.

Among secondary outcomes, stroke risk increased with all NSAIDs in 26 trials that reported 377 strokes. The increased risk was significant with four of the drugs, roughly doubling with naproxen and tripling with ibuprofen, diclofenac, etoricoxib, or lumiracoxib, compared with placebo.

Twenty-six trials reported 312 deaths from cardiovascular disease, accounting for 46% of all deaths in the trials. All NSAIDs except naproxen were associated with higher risk for cardiovascular death, which increased by 58% with rofecoxib, roughly doubled with ibuprofen, celecoxib, or lumiracoxib, and increased approximately fourfold with diclofenac or etoricoxib, compared with placebo.

All the NSAIDs were associated with increased risk for death from any cause, compared with placebo, and the increase was significant for all except naproxen. There were 676 deaths from any cause in 28 trials, and the risk of death roughly doubled with any of the other six NSAIDs.

Looking at a composite of nonfatal MI, nonfatal stroke, or cardiovascular death in 30 trials that reported 1,091 composite events, the risk increased with all the NSAIDs and increased significantly with all but naproxen.

View on the News

Time to Reevaluate NSAIDs

The cardiotoxicity of NSAIDs is particularly worrisome because many patients have both cardiovascular disease and musculoskeletal disease, Wayne A. Ray, Ph.D., noted in an editorial accompanying Dr. Trelle's study (BMJ Jan. 11, 2011;342:c6618 [doi:10.1136/bmj. c6618]).

What Dr. Trelle's study adds to the existing literature on NSAIDs is the potentially powerful technique known as network meta-analysis, which can extract more information from the data when certain assumptions are met, compared with traditional analyses, he wrote. The strength of the technique is that it uses all of the data, but it has some inherent weaknesses that should inspire caution when interpreting estimates based on indirect comparisons, explained Dr. Ray.

For example, no large, placebo-controlled trials compared etoricoxib vs. placebo. Risks of etoricoxib vs. placebo were estimated based on a chain of direct comparisons in separate trials – etoricoxib vs. diclofenac; diclofenac vs. rofecoxib or celecoxib, and finally rofecoxib or celecoxib vs. placebo.

Based on all the studies, what are the best strategies for clinicians who are considering NSAIDs for patients at high risk of cardiovascular disease? Avoid COX-2 inhibitors, especially in higher doses, Dr. Ray advised. Avoid diclofenac. Remember that ibuprofen may attenuate the antiplatelet effects of aspirin.

For now, naproxen seems to be the safest NSAID in terms of cardiovascular risk.

With any NSAID, consider also prescribing gastroprotective drugs.

NSAIDs are not the only option for treatment of musculoskeletal symptoms. Clinicians also prescribe paracetamol, low-dose opioid analgesics, and newer drugs, but without large-scale comparison studies, it's impossible to tell which is best for both efficacy and safety, Dr. Ray wrote. “Perhaps it is time for a larger, more systematic evaluation of a broader range of alternatives,” he suggested.

DR. WAYNE A. RAY is a professor and director of pharmacoepidemiology at Vanderbilt University, Nashville, Tenn. Dr. Ray has received financial support from Pfizer, was a paid expert witness in a lawsuit by the state of Texas against Merck, and is a paid expert in an insurance company action against the maker of Prempro.

Major Finding: Each of seven NSAIDs was associated with significantly increased risk for MI, stroke, or death from cardiovascular disease, compared with placebo.

Data Source: Network meta-analysis of 31 large, randomized controlled trials comparing any NSAID with other NSAIDs or placebo in 116,429 patients with 117,218 patient-years of follow-up.

Disclosures: The Swiss National Science Foundation funded the study. The investigators reported having no conflicts of interest.

Each of seven NSAIDs was associated with significantly increased risk for MI, stroke, or death from cardiovascular disease, compared with placebo, in the most comprehensive meta-analysis of the subject so far.

The relative risks with any individual NSAID, compared with placebo, often were double, triple, or quadruple the risk with placebo, the study found. The absolute numbers of MIs and other cardiovascular outcomes were small, but the network meta-analysis design of the study “provides the best available evidence on the safety of this class of drugs,” Dr. Sven Trelle and his associates reported.

Contrary to some previous reports, the current study also found no suggestion that this increased cardiovascular risk is specific to cyclo-oxygenase-2 (COX-2) inhibitors. Therefore the use of all NSAIDs – and the over-the-counter availability of some of them – should be reconsidered, Dr. Trelle stated in a report published online by BMJ (Jan. 11, 2011;342:c7086[doi/10.1136/bmj.c7086]).

Dr. Trelle of the University of Bern, Switzerland, acknowledged that therapeutic options for chronic musculoskeletal pain are limited, but cautioned that “cardiovascular risk needs to be taken into account when prescribing” any NSAID.

The meta-analysis included any large, randomized controlled trials comparing any NSAID with other NSAIDs or placebo. Data were available for naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, and lumiracoxib. The risk for a cardiovascular event had to increase by more than 30% to be considered significant.

Overall, naproxen appeared to be the least harmful NSAID in terms of cardiovascular outcomes. Risks were greatest with ibuprofen, diclofenac, etoricoxib, and lumiracoxib.

Four NSAIDs were associated with significantly increased risk for myocardial infarction (the primary outcome in the current analysis) in 29 of the trials that reported 554 MIs. The relative risk for MI doubled with rofecoxib or lumiracoxib, was 35% higher with celecoxib, and was 61% higher with ibuprofen, compared with placebo. Evidence was lacking for increased MI risk with the other three NSAIDs.

Among secondary outcomes, stroke risk increased with all NSAIDs in 26 trials that reported 377 strokes. The increased risk was significant with four of the drugs, roughly doubling with naproxen and tripling with ibuprofen, diclofenac, etoricoxib, or lumiracoxib, compared with placebo.

Twenty-six trials reported 312 deaths from cardiovascular disease, accounting for 46% of all deaths in the trials. All NSAIDs except naproxen were associated with higher risk for cardiovascular death, which increased by 58% with rofecoxib, roughly doubled with ibuprofen, celecoxib, or lumiracoxib, and increased approximately fourfold with diclofenac or etoricoxib, compared with placebo.

All the NSAIDs were associated with increased risk for death from any cause, compared with placebo, and the increase was significant for all except naproxen. There were 676 deaths from any cause in 28 trials, and the risk of death roughly doubled with any of the other six NSAIDs.

Looking at a composite of nonfatal MI, nonfatal stroke, or cardiovascular death in 30 trials that reported 1,091 composite events, the risk increased with all the NSAIDs and increased significantly with all but naproxen.

View on the News

Time to Reevaluate NSAIDs

The cardiotoxicity of NSAIDs is particularly worrisome because many patients have both cardiovascular disease and musculoskeletal disease, Wayne A. Ray, Ph.D., noted in an editorial accompanying Dr. Trelle's study (BMJ Jan. 11, 2011;342:c6618 [doi:10.1136/bmj. c6618]).

What Dr. Trelle's study adds to the existing literature on NSAIDs is the potentially powerful technique known as network meta-analysis, which can extract more information from the data when certain assumptions are met, compared with traditional analyses, he wrote. The strength of the technique is that it uses all of the data, but it has some inherent weaknesses that should inspire caution when interpreting estimates based on indirect comparisons, explained Dr. Ray.

For example, no large, placebo-controlled trials compared etoricoxib vs. placebo. Risks of etoricoxib vs. placebo were estimated based on a chain of direct comparisons in separate trials – etoricoxib vs. diclofenac; diclofenac vs. rofecoxib or celecoxib, and finally rofecoxib or celecoxib vs. placebo.

Based on all the studies, what are the best strategies for clinicians who are considering NSAIDs for patients at high risk of cardiovascular disease? Avoid COX-2 inhibitors, especially in higher doses, Dr. Ray advised. Avoid diclofenac. Remember that ibuprofen may attenuate the antiplatelet effects of aspirin.

For now, naproxen seems to be the safest NSAID in terms of cardiovascular risk.

With any NSAID, consider also prescribing gastroprotective drugs.

NSAIDs are not the only option for treatment of musculoskeletal symptoms. Clinicians also prescribe paracetamol, low-dose opioid analgesics, and newer drugs, but without large-scale comparison studies, it's impossible to tell which is best for both efficacy and safety, Dr. Ray wrote. “Perhaps it is time for a larger, more systematic evaluation of a broader range of alternatives,” he suggested.

DR. WAYNE A. RAY is a professor and director of pharmacoepidemiology at Vanderbilt University, Nashville, Tenn. Dr. Ray has received financial support from Pfizer, was a paid expert witness in a lawsuit by the state of Texas against Merck, and is a paid expert in an insurance company action against the maker of Prempro.

Major Finding: In the first 3 months, the rate of bone loss among patients with early RA who were treated with intra-articular corticosteroid injections plus methotrexate vs. methotrexate alone was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Data Source: A study of 40 patients who were treated for 12 months.

Disclosures: The researchers stated that they had no relevant financial disclosures to make.

Patients with early rheumatoid arthritis who were on methotrexate and received intra-articular corticosteroid injections into inflamed metacarpophalangeal joints for 3 months lost less periarticular density than did those who received methotrexate alone, results from a small study demonstrated.

The finding “supports the concept that, in conditions where inflammation dominates such as early RA, treating inflammation is more important than the negative effect of corticosteroids on bone,” reported researchers led by Dr. Glenn Haugeberg.

Dr. Haugeberg, professor of neuroscience at the Norwegian University of Science and Technology, Trondheim, and a member of the department of rheumatology at Sørlandet Hospital in Kristiansand (Norway), and his associates at two clinical centers in the United Kingdom treated 19 early RA patients with methotrexate alone and 21 with methotrexate plus intra-articular corticosteroid injections for 3 months. Over the next 9 months, all 40 patients received methotrexate plus intra-articular corticosteroid injections.

To assess the effect of treatment on bone loss, the researchers used MRI of the metacarpophalangeal joints of the dominant hand (that is, MCP joints 2-5) at baseline and 3 and 12 months, as well as DXA (dual-energy x-ray absorptiometry) images of both hands at baseline and 3, 6, and 12 months (Ann. Rheum. Dis. 2011;70:184-7). They used linear regression analysis to determine the association between reduction in bone mineral density and demographic and disease variables, adjusting for treatment group.

The mean age of patients was 54 years, and 55% were women. In the first 3 months of the study, patients in the group who received methotrexate plus intra-articular-corticosteroid injections experienced significantly lower rates of bone loss in MCP joints 2-5 than did their counterparts in the methotrexate-only group. The rate of bone loss was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Bone loss in the hand overall was less pronounced over the same time period (−1.53% among patients who received methotrexate plus intra-articular corticosteroid injections, compared with −2.42% among those in the methotrexate-only group).

In months 3-12, when all patients received intra-articular corticosteroid injections, only minor, nonsignificant differences in the rate of bone loss were observed between the two groups.

“Data from the current study suggest that bone loss may be arrested by intra-articular corticosteroid injections more effectively in periarticular regions than in the whole hand,” the researchers wrote.

In discussing their findings, the investigators wrote that the “results from the hand bone density studies also suggest that prednisolone is equivalent to [anti–tumor necrosis factor] treatment in reducing the rate of hand bone loss.

From a practical point of view, local administration of corticosteroids may be better than systemic administration as the drug is administered at the target site of the inflammatory process and is not disseminated throughout the body,” they wrote.

Major Finding: In the first 3 months, the rate of bone loss among patients with early RA who were treated with intra-articular corticosteroid injections plus methotrexate vs. methotrexate alone was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Data Source: A study of 40 patients who were treated for 12 months.

Disclosures: The researchers stated that they had no relevant financial disclosures to make.

Patients with early rheumatoid arthritis who were on methotrexate and received intra-articular corticosteroid injections into inflamed metacarpophalangeal joints for 3 months lost less periarticular density than did those who received methotrexate alone, results from a small study demonstrated.

The finding “supports the concept that, in conditions where inflammation dominates such as early RA, treating inflammation is more important than the negative effect of corticosteroids on bone,” reported researchers led by Dr. Glenn Haugeberg.

Dr. Haugeberg, professor of neuroscience at the Norwegian University of Science and Technology, Trondheim, and a member of the department of rheumatology at Sørlandet Hospital in Kristiansand (Norway), and his associates at two clinical centers in the United Kingdom treated 19 early RA patients with methotrexate alone and 21 with methotrexate plus intra-articular corticosteroid injections for 3 months. Over the next 9 months, all 40 patients received methotrexate plus intra-articular corticosteroid injections.

To assess the effect of treatment on bone loss, the researchers used MRI of the metacarpophalangeal joints of the dominant hand (that is, MCP joints 2-5) at baseline and 3 and 12 months, as well as DXA (dual-energy x-ray absorptiometry) images of both hands at baseline and 3, 6, and 12 months (Ann. Rheum. Dis. 2011;70:184-7). They used linear regression analysis to determine the association between reduction in bone mineral density and demographic and disease variables, adjusting for treatment group.

The mean age of patients was 54 years, and 55% were women. In the first 3 months of the study, patients in the group who received methotrexate plus intra-articular-corticosteroid injections experienced significantly lower rates of bone loss in MCP joints 2-5 than did their counterparts in the methotrexate-only group. The rate of bone loss was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Bone loss in the hand overall was less pronounced over the same time period (−1.53% among patients who received methotrexate plus intra-articular corticosteroid injections, compared with −2.42% among those in the methotrexate-only group).

In months 3-12, when all patients received intra-articular corticosteroid injections, only minor, nonsignificant differences in the rate of bone loss were observed between the two groups.

“Data from the current study suggest that bone loss may be arrested by intra-articular corticosteroid injections more effectively in periarticular regions than in the whole hand,” the researchers wrote.

In discussing their findings, the investigators wrote that the “results from the hand bone density studies also suggest that prednisolone is equivalent to [anti–tumor necrosis factor] treatment in reducing the rate of hand bone loss.

From a practical point of view, local administration of corticosteroids may be better than systemic administration as the drug is administered at the target site of the inflammatory process and is not disseminated throughout the body,” they wrote.

Major Finding: In the first 3 months, the rate of bone loss among patients with early RA who were treated with intra-articular corticosteroid injections plus methotrexate vs. methotrexate alone was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Data Source: A study of 40 patients who were treated for 12 months.

Disclosures: The researchers stated that they had no relevant financial disclosures to make.

Patients with early rheumatoid arthritis who were on methotrexate and received intra-articular corticosteroid injections into inflamed metacarpophalangeal joints for 3 months lost less periarticular density than did those who received methotrexate alone, results from a small study demonstrated.

The finding “supports the concept that, in conditions where inflammation dominates such as early RA, treating inflammation is more important than the negative effect of corticosteroids on bone,” reported researchers led by Dr. Glenn Haugeberg.

Dr. Haugeberg, professor of neuroscience at the Norwegian University of Science and Technology, Trondheim, and a member of the department of rheumatology at Sørlandet Hospital in Kristiansand (Norway), and his associates at two clinical centers in the United Kingdom treated 19 early RA patients with methotrexate alone and 21 with methotrexate plus intra-articular corticosteroid injections for 3 months. Over the next 9 months, all 40 patients received methotrexate plus intra-articular corticosteroid injections.

To assess the effect of treatment on bone loss, the researchers used MRI of the metacarpophalangeal joints of the dominant hand (that is, MCP joints 2-5) at baseline and 3 and 12 months, as well as DXA (dual-energy x-ray absorptiometry) images of both hands at baseline and 3, 6, and 12 months (Ann. Rheum. Dis. 2011;70:184-7). They used linear regression analysis to determine the association between reduction in bone mineral density and demographic and disease variables, adjusting for treatment group.

The mean age of patients was 54 years, and 55% were women. In the first 3 months of the study, patients in the group who received methotrexate plus intra-articular-corticosteroid injections experienced significantly lower rates of bone loss in MCP joints 2-5 than did their counterparts in the methotrexate-only group. The rate of bone loss was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Bone loss in the hand overall was less pronounced over the same time period (−1.53% among patients who received methotrexate plus intra-articular corticosteroid injections, compared with −2.42% among those in the methotrexate-only group).

In months 3-12, when all patients received intra-articular corticosteroid injections, only minor, nonsignificant differences in the rate of bone loss were observed between the two groups.

“Data from the current study suggest that bone loss may be arrested by intra-articular corticosteroid injections more effectively in periarticular regions than in the whole hand,” the researchers wrote.

In discussing their findings, the investigators wrote that the “results from the hand bone density studies also suggest that prednisolone is equivalent to [anti–tumor necrosis factor] treatment in reducing the rate of hand bone loss.

From a practical point of view, local administration of corticosteroids may be better than systemic administration as the drug is administered at the target site of the inflammatory process and is not disseminated throughout the body,” they wrote.

ATLANTA — Use of tumor necrosis factor inhibitors was associated with a lower rate of Alzheimer's disease in patients with rheumatoid arthritis.

The finding was seen in a nested case-control study. TNF blockers were associated with a 55% reduction in the risk of incident Alzheimer's dementia after adjustment for the presence of known potential risk factors for vascular dementia, including hypertension, hyperlipidemia, diabetes, peripheral vascular disease, and coronary artery disease, said Dr. Richard C. Chou of Dartmouth-Hitchcock Medical Center in Milton, Mass.

Dr. Chou and his colleagues identified 41,109 patients with RA in a commercially insured cohort of 8.5 million adults. Among the RA patients, 458 also had a diagnosis of Alzheimer's disease.

The overall prevalence of dementia in RA patients was 1.11%; the overall prevalence in the cohort without RA was 0.14%.

Exposure to three specific anti-TNF drugs – infliximab, etanercept, and adalimumab – was examined, as was exposure to sulfasalazine, prednisone, and rituximab.

Use of the anti-TNF agents as a group was significantly associated with a reduced risk of Alzheimer's dementia, Dr. Chou said. When the anti-TNF agents were analyzed individually, only etanercept was significantly associated with reduced risk. Etanercept was associated with about a 70% reduction in the risk of Alzheimer's dementia.

Dr. Chou said he had no relevant financial disclosures.

ATLANTA — Use of tumor necrosis factor inhibitors was associated with a lower rate of Alzheimer's disease in patients with rheumatoid arthritis.

The finding was seen in a nested case-control study. TNF blockers were associated with a 55% reduction in the risk of incident Alzheimer's dementia after adjustment for the presence of known potential risk factors for vascular dementia, including hypertension, hyperlipidemia, diabetes, peripheral vascular disease, and coronary artery disease, said Dr. Richard C. Chou of Dartmouth-Hitchcock Medical Center in Milton, Mass.

Dr. Chou and his colleagues identified 41,109 patients with RA in a commercially insured cohort of 8.5 million adults. Among the RA patients, 458 also had a diagnosis of Alzheimer's disease.

The overall prevalence of dementia in RA patients was 1.11%; the overall prevalence in the cohort without RA was 0.14%.

Exposure to three specific anti-TNF drugs – infliximab, etanercept, and adalimumab – was examined, as was exposure to sulfasalazine, prednisone, and rituximab.

Use of the anti-TNF agents as a group was significantly associated with a reduced risk of Alzheimer's dementia, Dr. Chou said. When the anti-TNF agents were analyzed individually, only etanercept was significantly associated with reduced risk. Etanercept was associated with about a 70% reduction in the risk of Alzheimer's dementia.

Dr. Chou said he had no relevant financial disclosures.

ATLANTA — Use of tumor necrosis factor inhibitors was associated with a lower rate of Alzheimer's disease in patients with rheumatoid arthritis.

The finding was seen in a nested case-control study. TNF blockers were associated with a 55% reduction in the risk of incident Alzheimer's dementia after adjustment for the presence of known potential risk factors for vascular dementia, including hypertension, hyperlipidemia, diabetes, peripheral vascular disease, and coronary artery disease, said Dr. Richard C. Chou of Dartmouth-Hitchcock Medical Center in Milton, Mass.

Dr. Chou and his colleagues identified 41,109 patients with RA in a commercially insured cohort of 8.5 million adults. Among the RA patients, 458 also had a diagnosis of Alzheimer's disease.

The overall prevalence of dementia in RA patients was 1.11%; the overall prevalence in the cohort without RA was 0.14%.

Exposure to three specific anti-TNF drugs – infliximab, etanercept, and adalimumab – was examined, as was exposure to sulfasalazine, prednisone, and rituximab.

Use of the anti-TNF agents as a group was significantly associated with a reduced risk of Alzheimer's dementia, Dr. Chou said. When the anti-TNF agents were analyzed individually, only etanercept was significantly associated with reduced risk. Etanercept was associated with about a 70% reduction in the risk of Alzheimer's dementia.

Dr. Chou said he had no relevant financial disclosures.

Major Finding: Opportunistic infections other than tuberculosis were 18 times more likely in patients on infliximab and 10 times more likely in patients on adalimumab, compared with patients on etanercept.

Data Source: A study of a French national registry of all patients with opportunistic infections while they were on TNFi agents, and case-control analysis of 43 patients with 45 non-TB opportunistic infections and 3 matched control patients without infection on anti-TNF agents.

Disclosures: Some of Dr. Salmon-Ceron's coauthors have been consultants or speakers for Abbott, Schering Plough, UCB, or Wyeth. The study was funded by Abbott, Schering Plough, Wyeth, and INSERM (Institut National de la Santé et de la Recherche Médicale.

Patients taking monoclonal anti–tumor necrosis factor antibody therapy were more likely than those on soluble TNF inhibiting therapy to develop opportunistic infections, other than tuberculosis, in a study of a French national registry.

Of the three TNFi agents used in France in 2004-2007, infliximab was associated with an 18-fold increased risk and adalimumab was associated with a 10-fold increased risk for nontuberculosis opportunistic infection, compared with etanercept, Dr. Dominique Salmon-Ceron and her associates reported. A higher incidence of opportunistic infection with infliximab or adalimumab, compared with etanercept, did not reach statistical significance because of the rarity of the infections. But the findings are supported by previous reports from the Food and Drug Administration, a Spanish registry, a study of 21 Japanese patients, and other accounts of a greater risk for opportunistic infection with infliximab, compared with etanercept, the investigators noted (Ann. Rheum. Dis. 2010 Dec. 21 [doi:10.1136/ard.2010. 137422]).

The study also identified a third risk factor: treatment with more than 10 mg/day of oral steroids or IV steroid boluses during the year before a diagnosis of non-TB opportunistic infection. Previous studies also identified this risk factor in patients with rheumatoid arthritis or systemic lupus erythematosus, so the current analysis “strengthens the need to avoid high doses of steroids for patients receiving anti-TNF agents,” reported Dr. Salmon-Ceron, who is professor of infectious diseases at Université René Descartes, Paris, as well as a member of the staff at of Hôpital Cochin in that city.

The data in the study come from the 3-year French RATIO (Research Axed on Tolerance of Biotherapies) registry and involved all cases in France of opportunistic infections in patients receiving TNFi agents for any reason. The case-control analysis matched each of the 43 case patients (with a total of 45 opportunistic infections) with 3 control patients who took TNFi agents without developing opportunistic infections.

Patients had been treated with TNFi agents for RA (26), spondyloarthritides (3), inflammatory colitis (8), psoriasis (1), or other problems (5). Four were on etanercept, 10 received adalimumab, and 39 were on infliximab.

Using pharmaceutical company data, the investigators estimated a total of 57,711 patient-years of use of TNFi therapy during the study period. They calculated an annual incidence of opportunistic infection in patients receiving TNFi agents as 152 per 100,000 patient-years, after adjusting for age and sex.

The incidence of opportunistic infection differed by TNFi agent, but the differences were not statistically significant (7 per 100,000 patient-years with etanercept, 62 per 100,000 patient-years with adalimumab, and 291 per 100,000 patient-years with infliximab). The rarity of opportunistic infections prevented statistical significance in comparisons.

Major Finding: Opportunistic infections other than tuberculosis were 18 times more likely in patients on infliximab and 10 times more likely in patients on adalimumab, compared with patients on etanercept.

Data Source: A study of a French national registry of all patients with opportunistic infections while they were on TNFi agents, and case-control analysis of 43 patients with 45 non-TB opportunistic infections and 3 matched control patients without infection on anti-TNF agents.

Disclosures: Some of Dr. Salmon-Ceron's coauthors have been consultants or speakers for Abbott, Schering Plough, UCB, or Wyeth. The study was funded by Abbott, Schering Plough, Wyeth, and INSERM (Institut National de la Santé et de la Recherche Médicale.

Patients taking monoclonal anti–tumor necrosis factor antibody therapy were more likely than those on soluble TNF inhibiting therapy to develop opportunistic infections, other than tuberculosis, in a study of a French national registry.

Of the three TNFi agents used in France in 2004-2007, infliximab was associated with an 18-fold increased risk and adalimumab was associated with a 10-fold increased risk for nontuberculosis opportunistic infection, compared with etanercept, Dr. Dominique Salmon-Ceron and her associates reported. A higher incidence of opportunistic infection with infliximab or adalimumab, compared with etanercept, did not reach statistical significance because of the rarity of the infections. But the findings are supported by previous reports from the Food and Drug Administration, a Spanish registry, a study of 21 Japanese patients, and other accounts of a greater risk for opportunistic infection with infliximab, compared with etanercept, the investigators noted (Ann. Rheum. Dis. 2010 Dec. 21 [doi:10.1136/ard.2010. 137422]).

The study also identified a third risk factor: treatment with more than 10 mg/day of oral steroids or IV steroid boluses during the year before a diagnosis of non-TB opportunistic infection. Previous studies also identified this risk factor in patients with rheumatoid arthritis or systemic lupus erythematosus, so the current analysis “strengthens the need to avoid high doses of steroids for patients receiving anti-TNF agents,” reported Dr. Salmon-Ceron, who is professor of infectious diseases at Université René Descartes, Paris, as well as a member of the staff at of Hôpital Cochin in that city.

The data in the study come from the 3-year French RATIO (Research Axed on Tolerance of Biotherapies) registry and involved all cases in France of opportunistic infections in patients receiving TNFi agents for any reason. The case-control analysis matched each of the 43 case patients (with a total of 45 opportunistic infections) with 3 control patients who took TNFi agents without developing opportunistic infections.

Patients had been treated with TNFi agents for RA (26), spondyloarthritides (3), inflammatory colitis (8), psoriasis (1), or other problems (5). Four were on etanercept, 10 received adalimumab, and 39 were on infliximab.

Using pharmaceutical company data, the investigators estimated a total of 57,711 patient-years of use of TNFi therapy during the study period. They calculated an annual incidence of opportunistic infection in patients receiving TNFi agents as 152 per 100,000 patient-years, after adjusting for age and sex.

The incidence of opportunistic infection differed by TNFi agent, but the differences were not statistically significant (7 per 100,000 patient-years with etanercept, 62 per 100,000 patient-years with adalimumab, and 291 per 100,000 patient-years with infliximab). The rarity of opportunistic infections prevented statistical significance in comparisons.

Major Finding: Opportunistic infections other than tuberculosis were 18 times more likely in patients on infliximab and 10 times more likely in patients on adalimumab, compared with patients on etanercept.

Data Source: A study of a French national registry of all patients with opportunistic infections while they were on TNFi agents, and case-control analysis of 43 patients with 45 non-TB opportunistic infections and 3 matched control patients without infection on anti-TNF agents.

Disclosures: Some of Dr. Salmon-Ceron's coauthors have been consultants or speakers for Abbott, Schering Plough, UCB, or Wyeth. The study was funded by Abbott, Schering Plough, Wyeth, and INSERM (Institut National de la Santé et de la Recherche Médicale.

Patients taking monoclonal anti–tumor necrosis factor antibody therapy were more likely than those on soluble TNF inhibiting therapy to develop opportunistic infections, other than tuberculosis, in a study of a French national registry.

Of the three TNFi agents used in France in 2004-2007, infliximab was associated with an 18-fold increased risk and adalimumab was associated with a 10-fold increased risk for nontuberculosis opportunistic infection, compared with etanercept, Dr. Dominique Salmon-Ceron and her associates reported. A higher incidence of opportunistic infection with infliximab or adalimumab, compared with etanercept, did not reach statistical significance because of the rarity of the infections. But the findings are supported by previous reports from the Food and Drug Administration, a Spanish registry, a study of 21 Japanese patients, and other accounts of a greater risk for opportunistic infection with infliximab, compared with etanercept, the investigators noted (Ann. Rheum. Dis. 2010 Dec. 21 [doi:10.1136/ard.2010. 137422]).

The study also identified a third risk factor: treatment with more than 10 mg/day of oral steroids or IV steroid boluses during the year before a diagnosis of non-TB opportunistic infection. Previous studies also identified this risk factor in patients with rheumatoid arthritis or systemic lupus erythematosus, so the current analysis “strengthens the need to avoid high doses of steroids for patients receiving anti-TNF agents,” reported Dr. Salmon-Ceron, who is professor of infectious diseases at Université René Descartes, Paris, as well as a member of the staff at of Hôpital Cochin in that city.

The data in the study come from the 3-year French RATIO (Research Axed on Tolerance of Biotherapies) registry and involved all cases in France of opportunistic infections in patients receiving TNFi agents for any reason. The case-control analysis matched each of the 43 case patients (with a total of 45 opportunistic infections) with 3 control patients who took TNFi agents without developing opportunistic infections.

Patients had been treated with TNFi agents for RA (26), spondyloarthritides (3), inflammatory colitis (8), psoriasis (1), or other problems (5). Four were on etanercept, 10 received adalimumab, and 39 were on infliximab.

Using pharmaceutical company data, the investigators estimated a total of 57,711 patient-years of use of TNFi therapy during the study period. They calculated an annual incidence of opportunistic infection in patients receiving TNFi agents as 152 per 100,000 patient-years, after adjusting for age and sex.

The incidence of opportunistic infection differed by TNFi agent, but the differences were not statistically significant (7 per 100,000 patient-years with etanercept, 62 per 100,000 patient-years with adalimumab, and 291 per 100,000 patient-years with infliximab). The rarity of opportunistic infections prevented statistical significance in comparisons.

Gregory Twachtman is a writer for “The Pink Sheet.” This news organization and “The Pink Sheet” are owned by Elsevier.

A comparative effectiveness study on drug therapies used to treat psoriatic arthritis in adults determined that evidence is insufficient to draw any conclusions.

“Overall, the data are quite limited and the evidence is insufficient to draw firm conclusions on comparative efficacy, effectiveness, and harms of either oral or biologic DMARDs [disease-modifying antirheumatic drugs] in this condition,” the draft report stated. AHRQ uploaded the draft report to the Effective Care portion of its Web site. The draft did not identify the lead investigators of the study.

AHRQ's findings come soon after the U.K.'s National Institute for Clinical Excellence rejected Simponi for the treatment of active and progressive psoriatic arthritis (PsA) in adults, claiming that evidence revealed that the Schering Plough/Johnson & Johnson product was not as effective as Pfizer's Enbrel.

The draft report noted that about 520,000 U.S. adults have PsA, with treatments aimed primarily at controlling pain and inflammation and, ultimately, at slowing or arresting the progression of joint destruction.

The study compared a variety of oral and biologic DMARDs, including Simponi (golimumab) and Enbrel (etanercept), as well as Sanofi-Synthelabo's Plaquenil (hydroxychloroquine), Sanofi-Aventis' Arava (leflunomide), methotrexate, sulfasalazine, Abbott's Humira (adalimumab), UCB's Cimzia (certolizumab) and J&J's Remicade (infliximab). Humira, Enbrel, Simponi, and Remicade are approved by FDA to be used in patients with PsA.

The comparative effectiveness study for PsA aimed to answer four key questions:

▸ Do drug therapies differ in their ability to reduce disease activity, to slow or limit progression of radiographic joint damage, or to maintain remission?

▸ Do drug therapies differ in their ability to improve patient-reported symptoms, functional capacity, or quality of life?

▸ Do drug therapies differ in harms, tolerability, adherence, or adverse effects?

▸ What are the comparative benefits and harms of drug therapies for PsA in subgroups of patients based on stage of disease, history of prior therapy, demographics, concomitant therapies, or comorbidities?

The limited evidence that surfaced during research addressed the first three questions but nothing could be found on the fourth.

The draft report noted that experts “have not arrived at consensus about the comparative effectiveness of corticosteroids, oral DMARDs, and biologic DMARDs for treating PsA. More importantly, it is unclear how the effectiveness and safety of different types of combination therapy compare. In addition, there is debate about how early in the disease process combination therapy should be initiated and whether patients will respond to a biologic agent if they have previously failed a different biologic agent.”

The draft report added that questions remain about the risks of these agents. There is also limited understanding of the benefits and risks regarding subpopulations, including ethnic minorities, the elderly, pregnant women, and patients with other comorbidities.

Gregory Twachtman is a writer for “The Pink Sheet.” This news organization and “The Pink Sheet” are owned by Elsevier.

A comparative effectiveness study on drug therapies used to treat psoriatic arthritis in adults determined that evidence is insufficient to draw any conclusions.

“Overall, the data are quite limited and the evidence is insufficient to draw firm conclusions on comparative efficacy, effectiveness, and harms of either oral or biologic DMARDs [disease-modifying antirheumatic drugs] in this condition,” the draft report stated. AHRQ uploaded the draft report to the Effective Care portion of its Web site. The draft did not identify the lead investigators of the study.

AHRQ's findings come soon after the U.K.'s National Institute for Clinical Excellence rejected Simponi for the treatment of active and progressive psoriatic arthritis (PsA) in adults, claiming that evidence revealed that the Schering Plough/Johnson & Johnson product was not as effective as Pfizer's Enbrel.

The draft report noted that about 520,000 U.S. adults have PsA, with treatments aimed primarily at controlling pain and inflammation and, ultimately, at slowing or arresting the progression of joint destruction.

The study compared a variety of oral and biologic DMARDs, including Simponi (golimumab) and Enbrel (etanercept), as well as Sanofi-Synthelabo's Plaquenil (hydroxychloroquine), Sanofi-Aventis' Arava (leflunomide), methotrexate, sulfasalazine, Abbott's Humira (adalimumab), UCB's Cimzia (certolizumab) and J&J's Remicade (infliximab). Humira, Enbrel, Simponi, and Remicade are approved by FDA to be used in patients with PsA.

The comparative effectiveness study for PsA aimed to answer four key questions:

▸ Do drug therapies differ in their ability to reduce disease activity, to slow or limit progression of radiographic joint damage, or to maintain remission?

▸ Do drug therapies differ in their ability to improve patient-reported symptoms, functional capacity, or quality of life?

▸ Do drug therapies differ in harms, tolerability, adherence, or adverse effects?

▸ What are the comparative benefits and harms of drug therapies for PsA in subgroups of patients based on stage of disease, history of prior therapy, demographics, concomitant therapies, or comorbidities?

The limited evidence that surfaced during research addressed the first three questions but nothing could be found on the fourth.

The draft report noted that experts “have not arrived at consensus about the comparative effectiveness of corticosteroids, oral DMARDs, and biologic DMARDs for treating PsA. More importantly, it is unclear how the effectiveness and safety of different types of combination therapy compare. In addition, there is debate about how early in the disease process combination therapy should be initiated and whether patients will respond to a biologic agent if they have previously failed a different biologic agent.”

The draft report added that questions remain about the risks of these agents. There is also limited understanding of the benefits and risks regarding subpopulations, including ethnic minorities, the elderly, pregnant women, and patients with other comorbidities.

Gregory Twachtman is a writer for “The Pink Sheet.” This news organization and “The Pink Sheet” are owned by Elsevier.

A comparative effectiveness study on drug therapies used to treat psoriatic arthritis in adults determined that evidence is insufficient to draw any conclusions.

“Overall, the data are quite limited and the evidence is insufficient to draw firm conclusions on comparative efficacy, effectiveness, and harms of either oral or biologic DMARDs [disease-modifying antirheumatic drugs] in this condition,” the draft report stated. AHRQ uploaded the draft report to the Effective Care portion of its Web site. The draft did not identify the lead investigators of the study.

AHRQ's findings come soon after the U.K.'s National Institute for Clinical Excellence rejected Simponi for the treatment of active and progressive psoriatic arthritis (PsA) in adults, claiming that evidence revealed that the Schering Plough/Johnson & Johnson product was not as effective as Pfizer's Enbrel.

The draft report noted that about 520,000 U.S. adults have PsA, with treatments aimed primarily at controlling pain and inflammation and, ultimately, at slowing or arresting the progression of joint destruction.

The study compared a variety of oral and biologic DMARDs, including Simponi (golimumab) and Enbrel (etanercept), as well as Sanofi-Synthelabo's Plaquenil (hydroxychloroquine), Sanofi-Aventis' Arava (leflunomide), methotrexate, sulfasalazine, Abbott's Humira (adalimumab), UCB's Cimzia (certolizumab) and J&J's Remicade (infliximab). Humira, Enbrel, Simponi, and Remicade are approved by FDA to be used in patients with PsA.

The comparative effectiveness study for PsA aimed to answer four key questions:

▸ Do drug therapies differ in their ability to reduce disease activity, to slow or limit progression of radiographic joint damage, or to maintain remission?

▸ Do drug therapies differ in their ability to improve patient-reported symptoms, functional capacity, or quality of life?

▸ Do drug therapies differ in harms, tolerability, adherence, or adverse effects?

▸ What are the comparative benefits and harms of drug therapies for PsA in subgroups of patients based on stage of disease, history of prior therapy, demographics, concomitant therapies, or comorbidities?

The limited evidence that surfaced during research addressed the first three questions but nothing could be found on the fourth.

The draft report noted that experts “have not arrived at consensus about the comparative effectiveness of corticosteroids, oral DMARDs, and biologic DMARDs for treating PsA. More importantly, it is unclear how the effectiveness and safety of different types of combination therapy compare. In addition, there is debate about how early in the disease process combination therapy should be initiated and whether patients will respond to a biologic agent if they have previously failed a different biologic agent.”

The draft report added that questions remain about the risks of these agents. There is also limited understanding of the benefits and risks regarding subpopulations, including ethnic minorities, the elderly, pregnant women, and patients with other comorbidities.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.

NEW YORK — Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68[suppl. 3]:544) showed that if patients who achieved remission with biologic therapy stopped that therapy, within 2 years 54% (62/115) stayed in drug-free remission, said Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three-quarters of those (39/53 or 34% of the original group) were brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) did not achieve remission again. “That number is too large,” said Dr. Yazici.

“Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA,” said Dr. Yazici. He advised against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year and 70% after the second year; by 3 years, only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from a mean of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). “The more biologics we have, the faster we switch, it seems,” commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy.

After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in most patients who use them, said Dr. Yazici. Data from registries tend to show no preference for one over another. He suggested that physicians allow at least a 3- to 6-month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK — Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68[suppl. 3]:544) showed that if patients who achieved remission with biologic therapy stopped that therapy, within 2 years 54% (62/115) stayed in drug-free remission, said Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three-quarters of those (39/53 or 34% of the original group) were brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) did not achieve remission again. “That number is too large,” said Dr. Yazici.

“Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA,” said Dr. Yazici. He advised against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year and 70% after the second year; by 3 years, only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from a mean of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). “The more biologics we have, the faster we switch, it seems,” commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy.

After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in most patients who use them, said Dr. Yazici. Data from registries tend to show no preference for one over another. He suggested that physicians allow at least a 3- to 6-month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK — Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68[suppl. 3]:544) showed that if patients who achieved remission with biologic therapy stopped that therapy, within 2 years 54% (62/115) stayed in drug-free remission, said Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three-quarters of those (39/53 or 34% of the original group) were brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) did not achieve remission again. “That number is too large,” said Dr. Yazici.

“Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA,” said Dr. Yazici. He advised against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year and 70% after the second year; by 3 years, only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from a mean of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). “The more biologics we have, the faster we switch, it seems,” commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy.

After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in most patients who use them, said Dr. Yazici. Data from registries tend to show no preference for one over another. He suggested that physicians allow at least a 3- to 6-month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK — Despite clinical advances, most rheumatology patient encounters are conducted much as they were 40 years ago, according to Dr. Theodore Pincus, who spoke at both the New York University Hospital for Joint Diseases meeting on Evidence-Based RA Therapy and the Fifth Annual Clinical Research Methodology Course.

And the patient loses out as a result.

Laboratory tests that are usually performed are not necessarily diagnostic, as 30%-40% of patients with rheumatoid arthritis have normal values of many measures (erythrocyte-sedimentation rate, C-reactive protein, and presence of rheumatoid factor and/or anti–cyclic citrullinated peptide antibodies). In addition, radiography and formal joint counts have significant clinical limitations, said Dr Pincus.

There is underuse of patient self-assessment tools such as the HAQ (Health Assessment Questionnaire) or MDHAQ (Multidimensional Health Assessment Questionnaire), both of which predict work disability, costs, and death from RA more precisely than do radiographs or laboratory tests, he said.

“I believe the MDHAQ-RAPID3 [Routine Assessment of Patient Index Data 3] should be incorporated into your infrastructure of care,” said Dr. Pincus, a clinical professor of medicine at New York University.

He described a 10-point checklist for all visits with patients who have rheumatic disease that is based on evidence and that relies more upon patient self-assessment and physician global assessment than it does on findings from joint counts, laboratory tests, or radiography.

Dr. Pincus proposed that physicians follow the 10-measure checklist during every clinical encounter to document patient status and quantify patient progress. (See box.) The checklist includes six self-report measures from the MDHAQ self-report questionnaire, including evaluation of function, pain, fatigue, and other symptoms; a patient global estimate of status; and the RAPID3 score. The four physician global measures include assessment of inflammation, damage, and changes that are noninflammatory, as well as a physician global estimate of status.

The MDHAQ is a version of the HAQ, which was the only patient self-assessment tool actually developed in the clinic, said Dr. Pincus. The MDHAQ has been modified to reflect escalating standards of rheumatology care, so currently patients are asked if they can walk 2 miles or participate in recreational activities or sports. Queries about sleep, anxiety, and depression have also been added. In addition, the MDHAQ provides a review of systems and recent medical history information.

According to Dr. Pincus, the HAQ and MDHAQ are better predictors than are joint count, laboratory tests, or radiographs of functional status, work disability, joint replacement surgery, or cost.

Dr. Pincus reported having no relevant financial disclosures.

Visit Checklist

In the 10-point checklist, the patient MDHAQ self-report questionnaire measures include the following:

▸ Function.

▸ Pain.

▸ Patient global estimate of status.

▸ RAPID3.

▸ Fatigue.

The physician global measures include the following:

▸ Physician global estimate of status.

▸ Inflammation.

▸ Damage.

▸ Noninflammatory/nondamage.

Source: Dr. Pincus

NEW YORK — Despite clinical advances, most rheumatology patient encounters are conducted much as they were 40 years ago, according to Dr. Theodore Pincus, who spoke at both the New York University Hospital for Joint Diseases meeting on Evidence-Based RA Therapy and the Fifth Annual Clinical Research Methodology Course.

And the patient loses out as a result.

Laboratory tests that are usually performed are not necessarily diagnostic, as 30%-40% of patients with rheumatoid arthritis have normal values of many measures (erythrocyte-sedimentation rate, C-reactive protein, and presence of rheumatoid factor and/or anti–cyclic citrullinated peptide antibodies). In addition, radiography and formal joint counts have significant clinical limitations, said Dr Pincus.

There is underuse of patient self-assessment tools such as the HAQ (Health Assessment Questionnaire) or MDHAQ (Multidimensional Health Assessment Questionnaire), both of which predict work disability, costs, and death from RA more precisely than do radiographs or laboratory tests, he said.

“I believe the MDHAQ-RAPID3 [Routine Assessment of Patient Index Data 3] should be incorporated into your infrastructure of care,” said Dr. Pincus, a clinical professor of medicine at New York University.

He described a 10-point checklist for all visits with patients who have rheumatic disease that is based on evidence and that relies more upon patient self-assessment and physician global assessment than it does on findings from joint counts, laboratory tests, or radiography.

Dr. Pincus proposed that physicians follow the 10-measure checklist during every clinical encounter to document patient status and quantify patient progress. (See box.) The checklist includes six self-report measures from the MDHAQ self-report questionnaire, including evaluation of function, pain, fatigue, and other symptoms; a patient global estimate of status; and the RAPID3 score. The four physician global measures include assessment of inflammation, damage, and changes that are noninflammatory, as well as a physician global estimate of status.

The MDHAQ is a version of the HAQ, which was the only patient self-assessment tool actually developed in the clinic, said Dr. Pincus. The MDHAQ has been modified to reflect escalating standards of rheumatology care, so currently patients are asked if they can walk 2 miles or participate in recreational activities or sports. Queries about sleep, anxiety, and depression have also been added. In addition, the MDHAQ provides a review of systems and recent medical history information.

According to Dr. Pincus, the HAQ and MDHAQ are better predictors than are joint count, laboratory tests, or radiographs of functional status, work disability, joint replacement surgery, or cost.

Dr. Pincus reported having no relevant financial disclosures.

Visit Checklist

In the 10-point checklist, the patient MDHAQ self-report questionnaire measures include the following:

▸ Function.

▸ Pain.

▸ Patient global estimate of status.

▸ RAPID3.

▸ Fatigue.

The physician global measures include the following:

▸ Physician global estimate of status.

▸ Inflammation.

▸ Damage.

▸ Noninflammatory/nondamage.

Source: Dr. Pincus

NEW YORK — Despite clinical advances, most rheumatology patient encounters are conducted much as they were 40 years ago, according to Dr. Theodore Pincus, who spoke at both the New York University Hospital for Joint Diseases meeting on Evidence-Based RA Therapy and the Fifth Annual Clinical Research Methodology Course.

And the patient loses out as a result.

Laboratory tests that are usually performed are not necessarily diagnostic, as 30%-40% of patients with rheumatoid arthritis have normal values of many measures (erythrocyte-sedimentation rate, C-reactive protein, and presence of rheumatoid factor and/or anti–cyclic citrullinated peptide antibodies). In addition, radiography and formal joint counts have significant clinical limitations, said Dr Pincus.

There is underuse of patient self-assessment tools such as the HAQ (Health Assessment Questionnaire) or MDHAQ (Multidimensional Health Assessment Questionnaire), both of which predict work disability, costs, and death from RA more precisely than do radiographs or laboratory tests, he said.

“I believe the MDHAQ-RAPID3 [Routine Assessment of Patient Index Data 3] should be incorporated into your infrastructure of care,” said Dr. Pincus, a clinical professor of medicine at New York University.

He described a 10-point checklist for all visits with patients who have rheumatic disease that is based on evidence and that relies more upon patient self-assessment and physician global assessment than it does on findings from joint counts, laboratory tests, or radiography.

Dr. Pincus proposed that physicians follow the 10-measure checklist during every clinical encounter to document patient status and quantify patient progress. (See box.) The checklist includes six self-report measures from the MDHAQ self-report questionnaire, including evaluation of function, pain, fatigue, and other symptoms; a patient global estimate of status; and the RAPID3 score. The four physician global measures include assessment of inflammation, damage, and changes that are noninflammatory, as well as a physician global estimate of status.

The MDHAQ is a version of the HAQ, which was the only patient self-assessment tool actually developed in the clinic, said Dr. Pincus. The MDHAQ has been modified to reflect escalating standards of rheumatology care, so currently patients are asked if they can walk 2 miles or participate in recreational activities or sports. Queries about sleep, anxiety, and depression have also been added. In addition, the MDHAQ provides a review of systems and recent medical history information.

According to Dr. Pincus, the HAQ and MDHAQ are better predictors than are joint count, laboratory tests, or radiographs of functional status, work disability, joint replacement surgery, or cost.

Dr. Pincus reported having no relevant financial disclosures.

Visit Checklist

In the 10-point checklist, the patient MDHAQ self-report questionnaire measures include the following:

▸ Function.

▸ Pain.

▸ Patient global estimate of status.

▸ RAPID3.

▸ Fatigue.

The physician global measures include the following:

▸ Physician global estimate of status.

▸ Inflammation.

▸ Damage.

▸ Noninflammatory/nondamage.

Source: Dr. Pincus