Rheumatoid Arthritis

CHICAGO — A new study confirms that acetaminophen is safe and effective for the treatment of pain associated with osteoarthritis of the knee and hip.

The results reinforce the American College of Rheumatology guidelines that recommend acetaminophen as a first-line therapy to relieve osteoarthritis (OA) pain, but contradict other studies that suggest acetaminophen may not be useful in treating OA pain.

“People were questioning whether acetaminophen had any role, and I think this study clearly shows it does,” lead author Roy D. Altman, M.D., reported in a poster presentation at the 2004 World Congress on Osteoarthritis. “People with mild to moderate pain with osteoarthritis often get adequate pain relief from acetaminophen.”

These findings are particularly relevant in the post-Vioxx environment, which has many patients concerned about the safety of some prescription arthritis medications.

ACR guidelines instruct physicians to start treatment with acetaminophen and then move on to nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors as the second and third lines of treatment, if pain control is not adequate.

Inadequate pain relief with acetaminophen may result from the adherence to the dosing schedule, said Dr. Altman at the meeting, which was sponsored by the Osteoarthritis Research Society International. The maximum recommended dosage is 1 g four times per day.

The study randomized 483 patients—who were at least 40 years old with moderate to moderately severe OA pain—to treatment with acetaminophen extended-release (ER) caplets at daily doses of 1,950 mg, 3,900 mg, or placebo. The long-acting formulation reduced the number of daily doses to just two for those taking the higher dose.

“One of the benefits of this dosing is that people will take it twice a day,” said Dr. Altman, of the division of rheumatology and arthritis at the University of California, Los Angeles. “Part of the problem is that people haven't been taking acetaminophen in doses that were adequate enough to give them pain relief because they start forgetting to take it.”

At 12 weeks, acetaminophen ER 3,900 mg/day was superior to placebo for all three primary efficacy end points: the average change in the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score (mean decrease of 25 mm vs. 19 mm), the WOMAC physical function score (mean decrease of 24 mm vs. 18 mm), and the patient's global assessment of therapy on the 0-4 Likert scale (mean change 2.11 vs. 1.81).

In contrast, acetaminophen ER at 1,950 mg/day was superior to placebo only in the patient's global assessment of therapy (mean change 2.09 vs. 1.81). “I think when you get into 2 grams a day, [the dosage] just isn't adequate, and this [study] shows that,” Dr. Altman said.

No serious drug-related adverse events occurred, which was supported by McNeil Consumer & Specialty Pharmaceuticals, the manufacturer of Tylenol.

“There has been an unnecessary battle between NSAIDs and acetaminophen,” Dr. Altman said. “Some areas work better than others. My feeling is that combination therapy has to be looked at more carefully.”

A second study presented at the meeting found that 4,000 mg/day of acetaminophen was safe for up to 12 months of use.

The double-blind study involved 571 patients with mild to moderately severe OA pain of the hip or knee who were randomized to treatment with 4,000 mg/day of acetaminophen or 750 mg/day of naproxen.

The WOMAC scores in pain, stiffness, and physical function among the 290 patients treated with acetaminophen were comparable to those of patients treated with naproxen, without any clinically important adverse effects, reported lead author Anthony Temple, M.D., vice president of medical affairs at McNeil Consumer & Specialty Pharmaceuticals in Fort Washington, Pa.

CHICAGO — A new study confirms that acetaminophen is safe and effective for the treatment of pain associated with osteoarthritis of the knee and hip.

The results reinforce the American College of Rheumatology guidelines that recommend acetaminophen as a first-line therapy to relieve osteoarthritis (OA) pain, but contradict other studies that suggest acetaminophen may not be useful in treating OA pain.

“People were questioning whether acetaminophen had any role, and I think this study clearly shows it does,” lead author Roy D. Altman, M.D., reported in a poster presentation at the 2004 World Congress on Osteoarthritis. “People with mild to moderate pain with osteoarthritis often get adequate pain relief from acetaminophen.”

These findings are particularly relevant in the post-Vioxx environment, which has many patients concerned about the safety of some prescription arthritis medications.

ACR guidelines instruct physicians to start treatment with acetaminophen and then move on to nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors as the second and third lines of treatment, if pain control is not adequate.

Inadequate pain relief with acetaminophen may result from the adherence to the dosing schedule, said Dr. Altman at the meeting, which was sponsored by the Osteoarthritis Research Society International. The maximum recommended dosage is 1 g four times per day.

The study randomized 483 patients—who were at least 40 years old with moderate to moderately severe OA pain—to treatment with acetaminophen extended-release (ER) caplets at daily doses of 1,950 mg, 3,900 mg, or placebo. The long-acting formulation reduced the number of daily doses to just two for those taking the higher dose.

“One of the benefits of this dosing is that people will take it twice a day,” said Dr. Altman, of the division of rheumatology and arthritis at the University of California, Los Angeles. “Part of the problem is that people haven't been taking acetaminophen in doses that were adequate enough to give them pain relief because they start forgetting to take it.”

At 12 weeks, acetaminophen ER 3,900 mg/day was superior to placebo for all three primary efficacy end points: the average change in the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score (mean decrease of 25 mm vs. 19 mm), the WOMAC physical function score (mean decrease of 24 mm vs. 18 mm), and the patient's global assessment of therapy on the 0-4 Likert scale (mean change 2.11 vs. 1.81).

In contrast, acetaminophen ER at 1,950 mg/day was superior to placebo only in the patient's global assessment of therapy (mean change 2.09 vs. 1.81). “I think when you get into 2 grams a day, [the dosage] just isn't adequate, and this [study] shows that,” Dr. Altman said.

No serious drug-related adverse events occurred, which was supported by McNeil Consumer & Specialty Pharmaceuticals, the manufacturer of Tylenol.

“There has been an unnecessary battle between NSAIDs and acetaminophen,” Dr. Altman said. “Some areas work better than others. My feeling is that combination therapy has to be looked at more carefully.”

A second study presented at the meeting found that 4,000 mg/day of acetaminophen was safe for up to 12 months of use.

The double-blind study involved 571 patients with mild to moderately severe OA pain of the hip or knee who were randomized to treatment with 4,000 mg/day of acetaminophen or 750 mg/day of naproxen.

The WOMAC scores in pain, stiffness, and physical function among the 290 patients treated with acetaminophen were comparable to those of patients treated with naproxen, without any clinically important adverse effects, reported lead author Anthony Temple, M.D., vice president of medical affairs at McNeil Consumer & Specialty Pharmaceuticals in Fort Washington, Pa.

CHICAGO — A new study confirms that acetaminophen is safe and effective for the treatment of pain associated with osteoarthritis of the knee and hip.

The results reinforce the American College of Rheumatology guidelines that recommend acetaminophen as a first-line therapy to relieve osteoarthritis (OA) pain, but contradict other studies that suggest acetaminophen may not be useful in treating OA pain.

“People were questioning whether acetaminophen had any role, and I think this study clearly shows it does,” lead author Roy D. Altman, M.D., reported in a poster presentation at the 2004 World Congress on Osteoarthritis. “People with mild to moderate pain with osteoarthritis often get adequate pain relief from acetaminophen.”

These findings are particularly relevant in the post-Vioxx environment, which has many patients concerned about the safety of some prescription arthritis medications.

ACR guidelines instruct physicians to start treatment with acetaminophen and then move on to nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors as the second and third lines of treatment, if pain control is not adequate.

Inadequate pain relief with acetaminophen may result from the adherence to the dosing schedule, said Dr. Altman at the meeting, which was sponsored by the Osteoarthritis Research Society International. The maximum recommended dosage is 1 g four times per day.

The study randomized 483 patients—who were at least 40 years old with moderate to moderately severe OA pain—to treatment with acetaminophen extended-release (ER) caplets at daily doses of 1,950 mg, 3,900 mg, or placebo. The long-acting formulation reduced the number of daily doses to just two for those taking the higher dose.

“One of the benefits of this dosing is that people will take it twice a day,” said Dr. Altman, of the division of rheumatology and arthritis at the University of California, Los Angeles. “Part of the problem is that people haven't been taking acetaminophen in doses that were adequate enough to give them pain relief because they start forgetting to take it.”

At 12 weeks, acetaminophen ER 3,900 mg/day was superior to placebo for all three primary efficacy end points: the average change in the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score (mean decrease of 25 mm vs. 19 mm), the WOMAC physical function score (mean decrease of 24 mm vs. 18 mm), and the patient's global assessment of therapy on the 0-4 Likert scale (mean change 2.11 vs. 1.81).

In contrast, acetaminophen ER at 1,950 mg/day was superior to placebo only in the patient's global assessment of therapy (mean change 2.09 vs. 1.81). “I think when you get into 2 grams a day, [the dosage] just isn't adequate, and this [study] shows that,” Dr. Altman said.

No serious drug-related adverse events occurred, which was supported by McNeil Consumer & Specialty Pharmaceuticals, the manufacturer of Tylenol.

“There has been an unnecessary battle between NSAIDs and acetaminophen,” Dr. Altman said. “Some areas work better than others. My feeling is that combination therapy has to be looked at more carefully.”

A second study presented at the meeting found that 4,000 mg/day of acetaminophen was safe for up to 12 months of use.

The double-blind study involved 571 patients with mild to moderately severe OA pain of the hip or knee who were randomized to treatment with 4,000 mg/day of acetaminophen or 750 mg/day of naproxen.

The WOMAC scores in pain, stiffness, and physical function among the 290 patients treated with acetaminophen were comparable to those of patients treated with naproxen, without any clinically important adverse effects, reported lead author Anthony Temple, M.D., vice president of medical affairs at McNeil Consumer & Specialty Pharmaceuticals in Fort Washington, Pa.

BUDAPEST, HUNGARY — Chloroquine therapy for patients with rheumatoid arthritis may lower levels of antibodies to oxidized low-density lipoprotein, and thus reduce the risk of cardiovascular disease, C.L.P. Mangueira, M.D., reported at the 4th International Congress on Autoimmunity.

Oxidized low-density lipoprotein (oxLDL) induces antibody production and the inflammatory process. These antibodies (anti-oxLDL) are also considered risk factors for cardiovascular disease.

In a study of 66 rheumatoid arthritis (RA) patients and 66 age-matched healthy controls, “we found an apparent association between the use of chloroquine and low levels of the antibodies to oxidized LDL,” said Dr. Mangueira of Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.

The researchers evaluated the levels of anti-oxLDL in RA patients by two different assays developed by Dr. Mangueira's group and compared them with those of the control group.

RA patients were using methotrexate, prednisone, sulfasalazine, chloroquine, and leflunomide.

“We found higher levels of anti-oxLDL in rheumatoid patients compared with the control group,” using both methods, Dr. Mangueira said. There was no statistical correlation between anti-oxLDL levels and disease severity, which was assessed using the Modified Disease Activity Score system, the erythrocyte sedimentation rate, and C-reactive protein.

The 22 RA patients on chloroquine therapy had lower levels of anti-ox-LDL than did RA patients with no chloroquine use. In addition, the RA patients taking chloroquine had lower levels of anti-apolipoprotein B peptides than did those not taking the drug.

BUDAPEST, HUNGARY — Chloroquine therapy for patients with rheumatoid arthritis may lower levels of antibodies to oxidized low-density lipoprotein, and thus reduce the risk of cardiovascular disease, C.L.P. Mangueira, M.D., reported at the 4th International Congress on Autoimmunity.

Oxidized low-density lipoprotein (oxLDL) induces antibody production and the inflammatory process. These antibodies (anti-oxLDL) are also considered risk factors for cardiovascular disease.

In a study of 66 rheumatoid arthritis (RA) patients and 66 age-matched healthy controls, “we found an apparent association between the use of chloroquine and low levels of the antibodies to oxidized LDL,” said Dr. Mangueira of Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.

The researchers evaluated the levels of anti-oxLDL in RA patients by two different assays developed by Dr. Mangueira's group and compared them with those of the control group.

RA patients were using methotrexate, prednisone, sulfasalazine, chloroquine, and leflunomide.

“We found higher levels of anti-oxLDL in rheumatoid patients compared with the control group,” using both methods, Dr. Mangueira said. There was no statistical correlation between anti-oxLDL levels and disease severity, which was assessed using the Modified Disease Activity Score system, the erythrocyte sedimentation rate, and C-reactive protein.

The 22 RA patients on chloroquine therapy had lower levels of anti-ox-LDL than did RA patients with no chloroquine use. In addition, the RA patients taking chloroquine had lower levels of anti-apolipoprotein B peptides than did those not taking the drug.

BUDAPEST, HUNGARY — Chloroquine therapy for patients with rheumatoid arthritis may lower levels of antibodies to oxidized low-density lipoprotein, and thus reduce the risk of cardiovascular disease, C.L.P. Mangueira, M.D., reported at the 4th International Congress on Autoimmunity.

Oxidized low-density lipoprotein (oxLDL) induces antibody production and the inflammatory process. These antibodies (anti-oxLDL) are also considered risk factors for cardiovascular disease.

In a study of 66 rheumatoid arthritis (RA) patients and 66 age-matched healthy controls, “we found an apparent association between the use of chloroquine and low levels of the antibodies to oxidized LDL,” said Dr. Mangueira of Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.

The researchers evaluated the levels of anti-oxLDL in RA patients by two different assays developed by Dr. Mangueira's group and compared them with those of the control group.

RA patients were using methotrexate, prednisone, sulfasalazine, chloroquine, and leflunomide.

“We found higher levels of anti-oxLDL in rheumatoid patients compared with the control group,” using both methods, Dr. Mangueira said. There was no statistical correlation between anti-oxLDL levels and disease severity, which was assessed using the Modified Disease Activity Score system, the erythrocyte sedimentation rate, and C-reactive protein.

The 22 RA patients on chloroquine therapy had lower levels of anti-ox-LDL than did RA patients with no chloroquine use. In addition, the RA patients taking chloroquine had lower levels of anti-apolipoprotein B peptides than did those not taking the drug.

BERLIN — Long-term low-dose glucocorticoid therapy has gotten an undeserved bad rap in terms of side effects, according to a new report by an expert panel.

Systemic corticosteroids can be likened to fine wine, Dr. Johannes W.J. Bijlsma said in summarizing the panel's findings at the annual European Congress of Rheumatology.

“We think that a little bit of glucocorticoids, like a glass of wine, may be beneficial for many people, whereas a lot of glucocorticoids, like a bottle of wine, is helpful to no one,” said Dr. Bijlsma, professor of rheumatology and clinical immunology at Utrecht (the Netherlands) University Medical Center.

He was one of a dozen prominent European and American rheumatologists and endocrinologists who met recently to review the literature on the side-effect profile of systemic corticosteroids at 7.5 mg/day or less when used for years at a time in patients with rheumatic diseases. All panelists had expertise in this area, having participated in randomized controlled trials or epidemiologic studies that addressed relevant safety issues. It seemed an appropriate time to address the side effects issue in light of recent evidence that low-dose steroids have a disease-modifying effect in rheumatoid arthritis, Dr. Bijlsma explained.

The panelists' first key finding was that despite the fact that doses of 7.5 mg/day or less are what are most commonly used in the everyday treatment of rheumatologic diseases, there are few studies looking at the associated side effects. The panel focused on five trials totaling more than 750 patients with early rheumatoid arthritis randomized to low-dose steroids or placebo for at least 1 year. Two of the studies—the West of Scotland Early Rheumatoid Arthritis Corticosteroid Trial (WOSERACT) and a German trial—aren't yet published.

The data demonstrated that the incidence of side effects associated with long-term low-dose steroid therapy was much lower than what many clinicians believe it to be, based upon rates quoted in many review articles and textbooks, sources that generally extrapolate from studies involving far higher doses.

It is often stated that long-term glucocorticoid therapy is associated with up to a 20% increased rate of new-onset hypertension.

But in the three randomized trials of long-term low-dose therapy that addressed this issue, new hypertension wasn't significantly more frequent than with placebo: 19 cases in 281 steroid-treated patients, compared with 12 cases among 276 on placebo.

Similarly, new-onset diabetes occurred in just 2 of 185 patients on long-term glucocorticoid therapy at 7.5 mg/day or less, compared with 3 of 186 on placebo, Dr. Bijlsma said.

In the five randomized trials collectively, bone mineral density after 1-4 years of low-dose steroid therapy didn't differ from placebo. Nor was there any increase in fractures with steroid therapy in four of the five studies. The outlier was the Utrecht study. It showed an increase in fractures after 3 years of steroid therapy. But this trial began in 1990, well before physicians began routinely employing preventive measures including calcium and vitamin D supplements and bisphosphonates in steroid-treated patients, as became standard practice in the more recent trials.

“Osteoporosis remains a danger, but it has become a manageable danger,” he said.

Treatment-related weight gain is a major concern among patients. The data documented a modest weight gain during 2 years of low-dose steroid therapy—an average of 1.4 kg more than with placebo. “But we should also recognize there's a catabolic process in early rheumatoid arthritis—and weight gain can be one of the signs patients are improving,” Dr. Bijlsma said.

Low-dose corticosteroid monotherapy wasn't associated with increased gastrointestinal side effects.

However, when used in combination with NSAIDs, the resultant increase in peptic ulcer disease was greater than with NSAIDs alone.

BERLIN — Long-term low-dose glucocorticoid therapy has gotten an undeserved bad rap in terms of side effects, according to a new report by an expert panel.

Systemic corticosteroids can be likened to fine wine, Dr. Johannes W.J. Bijlsma said in summarizing the panel's findings at the annual European Congress of Rheumatology.

“We think that a little bit of glucocorticoids, like a glass of wine, may be beneficial for many people, whereas a lot of glucocorticoids, like a bottle of wine, is helpful to no one,” said Dr. Bijlsma, professor of rheumatology and clinical immunology at Utrecht (the Netherlands) University Medical Center.

He was one of a dozen prominent European and American rheumatologists and endocrinologists who met recently to review the literature on the side-effect profile of systemic corticosteroids at 7.5 mg/day or less when used for years at a time in patients with rheumatic diseases. All panelists had expertise in this area, having participated in randomized controlled trials or epidemiologic studies that addressed relevant safety issues. It seemed an appropriate time to address the side effects issue in light of recent evidence that low-dose steroids have a disease-modifying effect in rheumatoid arthritis, Dr. Bijlsma explained.

The panelists' first key finding was that despite the fact that doses of 7.5 mg/day or less are what are most commonly used in the everyday treatment of rheumatologic diseases, there are few studies looking at the associated side effects. The panel focused on five trials totaling more than 750 patients with early rheumatoid arthritis randomized to low-dose steroids or placebo for at least 1 year. Two of the studies—the West of Scotland Early Rheumatoid Arthritis Corticosteroid Trial (WOSERACT) and a German trial—aren't yet published.

The data demonstrated that the incidence of side effects associated with long-term low-dose steroid therapy was much lower than what many clinicians believe it to be, based upon rates quoted in many review articles and textbooks, sources that generally extrapolate from studies involving far higher doses.

It is often stated that long-term glucocorticoid therapy is associated with up to a 20% increased rate of new-onset hypertension.

But in the three randomized trials of long-term low-dose therapy that addressed this issue, new hypertension wasn't significantly more frequent than with placebo: 19 cases in 281 steroid-treated patients, compared with 12 cases among 276 on placebo.

Similarly, new-onset diabetes occurred in just 2 of 185 patients on long-term glucocorticoid therapy at 7.5 mg/day or less, compared with 3 of 186 on placebo, Dr. Bijlsma said.

In the five randomized trials collectively, bone mineral density after 1-4 years of low-dose steroid therapy didn't differ from placebo. Nor was there any increase in fractures with steroid therapy in four of the five studies. The outlier was the Utrecht study. It showed an increase in fractures after 3 years of steroid therapy. But this trial began in 1990, well before physicians began routinely employing preventive measures including calcium and vitamin D supplements and bisphosphonates in steroid-treated patients, as became standard practice in the more recent trials.

“Osteoporosis remains a danger, but it has become a manageable danger,” he said.

Treatment-related weight gain is a major concern among patients. The data documented a modest weight gain during 2 years of low-dose steroid therapy—an average of 1.4 kg more than with placebo. “But we should also recognize there's a catabolic process in early rheumatoid arthritis—and weight gain can be one of the signs patients are improving,” Dr. Bijlsma said.

Low-dose corticosteroid monotherapy wasn't associated with increased gastrointestinal side effects.

However, when used in combination with NSAIDs, the resultant increase in peptic ulcer disease was greater than with NSAIDs alone.

BERLIN — Long-term low-dose glucocorticoid therapy has gotten an undeserved bad rap in terms of side effects, according to a new report by an expert panel.

Systemic corticosteroids can be likened to fine wine, Dr. Johannes W.J. Bijlsma said in summarizing the panel's findings at the annual European Congress of Rheumatology.

“We think that a little bit of glucocorticoids, like a glass of wine, may be beneficial for many people, whereas a lot of glucocorticoids, like a bottle of wine, is helpful to no one,” said Dr. Bijlsma, professor of rheumatology and clinical immunology at Utrecht (the Netherlands) University Medical Center.

He was one of a dozen prominent European and American rheumatologists and endocrinologists who met recently to review the literature on the side-effect profile of systemic corticosteroids at 7.5 mg/day or less when used for years at a time in patients with rheumatic diseases. All panelists had expertise in this area, having participated in randomized controlled trials or epidemiologic studies that addressed relevant safety issues. It seemed an appropriate time to address the side effects issue in light of recent evidence that low-dose steroids have a disease-modifying effect in rheumatoid arthritis, Dr. Bijlsma explained.

The panelists' first key finding was that despite the fact that doses of 7.5 mg/day or less are what are most commonly used in the everyday treatment of rheumatologic diseases, there are few studies looking at the associated side effects. The panel focused on five trials totaling more than 750 patients with early rheumatoid arthritis randomized to low-dose steroids or placebo for at least 1 year. Two of the studies—the West of Scotland Early Rheumatoid Arthritis Corticosteroid Trial (WOSERACT) and a German trial—aren't yet published.

The data demonstrated that the incidence of side effects associated with long-term low-dose steroid therapy was much lower than what many clinicians believe it to be, based upon rates quoted in many review articles and textbooks, sources that generally extrapolate from studies involving far higher doses.

It is often stated that long-term glucocorticoid therapy is associated with up to a 20% increased rate of new-onset hypertension.

But in the three randomized trials of long-term low-dose therapy that addressed this issue, new hypertension wasn't significantly more frequent than with placebo: 19 cases in 281 steroid-treated patients, compared with 12 cases among 276 on placebo.

Similarly, new-onset diabetes occurred in just 2 of 185 patients on long-term glucocorticoid therapy at 7.5 mg/day or less, compared with 3 of 186 on placebo, Dr. Bijlsma said.

In the five randomized trials collectively, bone mineral density after 1-4 years of low-dose steroid therapy didn't differ from placebo. Nor was there any increase in fractures with steroid therapy in four of the five studies. The outlier was the Utrecht study. It showed an increase in fractures after 3 years of steroid therapy. But this trial began in 1990, well before physicians began routinely employing preventive measures including calcium and vitamin D supplements and bisphosphonates in steroid-treated patients, as became standard practice in the more recent trials.

“Osteoporosis remains a danger, but it has become a manageable danger,” he said.

Treatment-related weight gain is a major concern among patients. The data documented a modest weight gain during 2 years of low-dose steroid therapy—an average of 1.4 kg more than with placebo. “But we should also recognize there's a catabolic process in early rheumatoid arthritis—and weight gain can be one of the signs patients are improving,” Dr. Bijlsma said.

Low-dose corticosteroid monotherapy wasn't associated with increased gastrointestinal side effects.

However, when used in combination with NSAIDs, the resultant increase in peptic ulcer disease was greater than with NSAIDs alone.

SAN ANTONIO — Postmarketing trial data indicate that at the standard dosage, infliximab is not associated with an excess risk of infection during the first year of therapy, but higher doses may be, David Yocum, M.D., reported at the annual meeting of the American College of Rheumatology.

Dr. Yocum's investigation included patients with a history of active or latent TB and found no evidence that the biologic therapy reactivated infection.

“I think this reaffirms the positive risk-benefit ratio of the approved dose of infliximab,” said Dr. Yocum, who presented the results of the safety trial, which was initiated by the manufacturer, Centocor, to satisfy Food and Drug Administration requirements.

From the outset, the trial was designed to include patients with comorbidities in an effort to discern the risks from therapy in a “real-life” clinical setting, as opposed to the typical study population, he added.

In the trial, 1,082 patients were divided nearly equally into three treatment arms. The first group of study participants received placebo and then crossed over to receive standard-dose infliximab, 3 mg/kg, at weeks 22, 26, 30, 38, and 46.

The second group received standard-dose infliximab until week 22, at which point the dosage increased by 1.5-mg/kg increments every 8 weeks, as deemed necessary. The third group received infliximab 10 mg/kg through week 46.

All patients continued to receive concomitant methotrexate at a dose of 25 mg/wk or greater.

During the first 22-week phase of the trial, the group treated with standard-dose infliximab had the same rate of serious infections as the methotrexate-only group (1.7%).

By comparison, the infection rate among patients treated at the 10-mg/kg dose was nearly three times higher (5.3%), said Dr. Yocum who conducted the study at the University of Arizona, Tucson.

During the entire 54-week trial, infection rates were equal among the group on placebo that started infliximab therapy at 22 weeks and the group taking standard-dose therapy with the option to increase the dosage (3.6% each).

By comparison, 8.9% of those patients on the 10-mg/kg dosage developed serious infections.

The data suggest that if and when infections do occur in patients on infliximab, they tend to occur early. In addition, dose escalation is not a factor as long as the dose remains below 10 mg/kg, Dr. Yocum said.

Of the 54 patients who took escalating doses, 93% needed only two increases (1.5 mg/kg each time), and only 7 patients required 9 mg/kg.

The most common serious infection, pneumonia, occurred in 1.5% of the group that started infliximab later and in 1.4% of the group with the option of increasing the dosage.

Pneumonia developed in 1.9% of the high-dose group.

The multicenter trial included patients who had a history of active or latent tuberculosis.

There was one case of tuberculosis in the group who started late, two cases in the group who escalated, and four cases in the high-dose group.

SAN ANTONIO — Postmarketing trial data indicate that at the standard dosage, infliximab is not associated with an excess risk of infection during the first year of therapy, but higher doses may be, David Yocum, M.D., reported at the annual meeting of the American College of Rheumatology.

Dr. Yocum's investigation included patients with a history of active or latent TB and found no evidence that the biologic therapy reactivated infection.

“I think this reaffirms the positive risk-benefit ratio of the approved dose of infliximab,” said Dr. Yocum, who presented the results of the safety trial, which was initiated by the manufacturer, Centocor, to satisfy Food and Drug Administration requirements.

From the outset, the trial was designed to include patients with comorbidities in an effort to discern the risks from therapy in a “real-life” clinical setting, as opposed to the typical study population, he added.

In the trial, 1,082 patients were divided nearly equally into three treatment arms. The first group of study participants received placebo and then crossed over to receive standard-dose infliximab, 3 mg/kg, at weeks 22, 26, 30, 38, and 46.

The second group received standard-dose infliximab until week 22, at which point the dosage increased by 1.5-mg/kg increments every 8 weeks, as deemed necessary. The third group received infliximab 10 mg/kg through week 46.

All patients continued to receive concomitant methotrexate at a dose of 25 mg/wk or greater.

During the first 22-week phase of the trial, the group treated with standard-dose infliximab had the same rate of serious infections as the methotrexate-only group (1.7%).

By comparison, the infection rate among patients treated at the 10-mg/kg dose was nearly three times higher (5.3%), said Dr. Yocum who conducted the study at the University of Arizona, Tucson.

During the entire 54-week trial, infection rates were equal among the group on placebo that started infliximab therapy at 22 weeks and the group taking standard-dose therapy with the option to increase the dosage (3.6% each).

By comparison, 8.9% of those patients on the 10-mg/kg dosage developed serious infections.

The data suggest that if and when infections do occur in patients on infliximab, they tend to occur early. In addition, dose escalation is not a factor as long as the dose remains below 10 mg/kg, Dr. Yocum said.

Of the 54 patients who took escalating doses, 93% needed only two increases (1.5 mg/kg each time), and only 7 patients required 9 mg/kg.

The most common serious infection, pneumonia, occurred in 1.5% of the group that started infliximab later and in 1.4% of the group with the option of increasing the dosage.

Pneumonia developed in 1.9% of the high-dose group.

The multicenter trial included patients who had a history of active or latent tuberculosis.

There was one case of tuberculosis in the group who started late, two cases in the group who escalated, and four cases in the high-dose group.

SAN ANTONIO — Postmarketing trial data indicate that at the standard dosage, infliximab is not associated with an excess risk of infection during the first year of therapy, but higher doses may be, David Yocum, M.D., reported at the annual meeting of the American College of Rheumatology.

Dr. Yocum's investigation included patients with a history of active or latent TB and found no evidence that the biologic therapy reactivated infection.

“I think this reaffirms the positive risk-benefit ratio of the approved dose of infliximab,” said Dr. Yocum, who presented the results of the safety trial, which was initiated by the manufacturer, Centocor, to satisfy Food and Drug Administration requirements.

From the outset, the trial was designed to include patients with comorbidities in an effort to discern the risks from therapy in a “real-life” clinical setting, as opposed to the typical study population, he added.

In the trial, 1,082 patients were divided nearly equally into three treatment arms. The first group of study participants received placebo and then crossed over to receive standard-dose infliximab, 3 mg/kg, at weeks 22, 26, 30, 38, and 46.

The second group received standard-dose infliximab until week 22, at which point the dosage increased by 1.5-mg/kg increments every 8 weeks, as deemed necessary. The third group received infliximab 10 mg/kg through week 46.

All patients continued to receive concomitant methotrexate at a dose of 25 mg/wk or greater.

During the first 22-week phase of the trial, the group treated with standard-dose infliximab had the same rate of serious infections as the methotrexate-only group (1.7%).

By comparison, the infection rate among patients treated at the 10-mg/kg dose was nearly three times higher (5.3%), said Dr. Yocum who conducted the study at the University of Arizona, Tucson.

During the entire 54-week trial, infection rates were equal among the group on placebo that started infliximab therapy at 22 weeks and the group taking standard-dose therapy with the option to increase the dosage (3.6% each).

By comparison, 8.9% of those patients on the 10-mg/kg dosage developed serious infections.

The data suggest that if and when infections do occur in patients on infliximab, they tend to occur early. In addition, dose escalation is not a factor as long as the dose remains below 10 mg/kg, Dr. Yocum said.

Of the 54 patients who took escalating doses, 93% needed only two increases (1.5 mg/kg each time), and only 7 patients required 9 mg/kg.

The most common serious infection, pneumonia, occurred in 1.5% of the group that started infliximab later and in 1.4% of the group with the option of increasing the dosage.

Pneumonia developed in 1.9% of the high-dose group.

The multicenter trial included patients who had a history of active or latent tuberculosis.

There was one case of tuberculosis in the group who started late, two cases in the group who escalated, and four cases in the high-dose group.