Nancy Walsh

NEW YORK — Racial disparities in access to health care will disappear only when adequate and representative samples of minorities participate in clinical trials, Winston Price, M.D., said at the annual meeting of the National Medical Association.

That disparities in delivery of health care exist is not in question. The Institute of Medicine report “Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare” revealed the extent of the problem, showing that disparities remain even after adjustment for factors such as insurance coverage and socioeconomic status.

But a widespread mistrust of the U.S. health care system among minorities—not least because of past abuses such as the Tuskegee Syphilis Study, in which blacks went untreated for many years despite the availability of effective therapy—has led to an unwillingness among African Americans to participate in the clinical trials that might directly benefit their own health.

An increasing understanding of genetic differences and racial differences in response to medications now makes it imperative that minorities be included and their needs addressed in the drug development process, said Dr. Price of the State University of New York Health Science Center, Brooklyn.

The experience with BiDil, a fixed-dose combination of isosorbide dinitrate and hydralazine approved specifically for the treatment of heart failure in black patients, shows it can be done (July 2005, p. 1).

“You had 1,050 African Americans who enrolled in the study, and the attrition rate was zero,” Dr. Price, who is also president of the NMA, said in a press briefing. “Every single one stayed with that study until completion. The drug was approved by the Food and Drug Administration on June 23, not because it was the right thing to do but because it was pure science and evidence based. All we're asking for is parity.”

Other model programs also are demonstrating that blacks can be recruited successfully, Christopher L. Edwards, Ph.D., said at the briefing. Programs that are successful tend to be well entrenched in the community; they have significant outreach and education and strong, ongoing relationships with local organizations such as churches and fraternities, Dr. Edwards said.

They do not pressure potential study participants, but rather provide information and allow patients to process the information at home and respond to the investigators when they are ready, he said.

Successful investigators are available to the community not only when recruiting; they are able to articulate the tangible benefits of participation. Dr. Edwards' program in the department of psychiatry at Duke University Medical Center, Durham, N.C., is an example.

“We make ourselves available for interviews on television, religious radio, and pop radio. In one creative marketing plan, we placed advertisements for one of our genetic studies on the side of 20 city buses, and have seen a significant number of patients responding.” he said. The overall strategy of information dissemination is to go where the patients are, and not to rely on them to come to us.

In the Duke program, the relevant stakeholders are at the table when recruiting programs are being designed. “If we are recruiting college students, we had students who sat on review panels and advisory boards to give us guidance as to what they would respond to, how, and in what setting,” Dr. Edwards said.

Another panel member, Rahn K. Bailey, M.D., said that throughout his career he has been interested in issues such as differences in drug metabolism between African Americans and other patients. For example, about 40% of black patients are slow or intermediate metabolizers of many psychiatric medications, said Dr. Bailey of the department of psychiatry and human behavior, University of Texas, Houston, and chair of the NMA psychiatry and behavioral sciences section.

Because of this, black patients tend to experience more toxicity, and efficacy may be compromised. “It's not surprising to me now that many of my patients over the years have had great difficulty getting better, relapsed a lot quicker, come back to the hospital frequently, and ended up in the legal system because of clinical issues that were not addressed medically,” he said.

“In psychiatry it's as if we did all our studies on inpatients and none on outpatients, or in suburban communities rather than inner cities. The distinctions are apparent and actually affect medical decision making,” said Dr. Bailey, adding that these issues also are relevant in cardiovascular medicine, neurology, ob.gyn., and other areas of medicine.

NEW YORK — Racial disparities in access to health care will disappear only when adequate and representative samples of minorities participate in clinical trials, Winston Price, M.D., said at the annual meeting of the National Medical Association.

That disparities in delivery of health care exist is not in question. The Institute of Medicine report “Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare” revealed the extent of the problem, showing that disparities remain even after adjustment for factors such as insurance coverage and socioeconomic status.

But a widespread mistrust of the U.S. health care system among minorities—not least because of past abuses such as the Tuskegee Syphilis Study, in which blacks went untreated for many years despite the availability of effective therapy—has led to an unwillingness among African Americans to participate in the clinical trials that might directly benefit their own health.

An increasing understanding of genetic differences and racial differences in response to medications now makes it imperative that minorities be included and their needs addressed in the drug development process, said Dr. Price of the State University of New York Health Science Center, Brooklyn.

The experience with BiDil, a fixed-dose combination of isosorbide dinitrate and hydralazine approved specifically for the treatment of heart failure in black patients, shows it can be done (July 2005, p. 1).

“You had 1,050 African Americans who enrolled in the study, and the attrition rate was zero,” Dr. Price, who is also president of the NMA, said in a press briefing. “Every single one stayed with that study until completion. The drug was approved by the Food and Drug Administration on June 23, not because it was the right thing to do but because it was pure science and evidence based. All we're asking for is parity.”

Other model programs also are demonstrating that blacks can be recruited successfully, Christopher L. Edwards, Ph.D., said at the briefing. Programs that are successful tend to be well entrenched in the community; they have significant outreach and education and strong, ongoing relationships with local organizations such as churches and fraternities, Dr. Edwards said.

They do not pressure potential study participants, but rather provide information and allow patients to process the information at home and respond to the investigators when they are ready, he said.

Successful investigators are available to the community not only when recruiting; they are able to articulate the tangible benefits of participation. Dr. Edwards' program in the department of psychiatry at Duke University Medical Center, Durham, N.C., is an example.

“We make ourselves available for interviews on television, religious radio, and pop radio. In one creative marketing plan, we placed advertisements for one of our genetic studies on the side of 20 city buses, and have seen a significant number of patients responding.” he said. The overall strategy of information dissemination is to go where the patients are, and not to rely on them to come to us.

In the Duke program, the relevant stakeholders are at the table when recruiting programs are being designed. “If we are recruiting college students, we had students who sat on review panels and advisory boards to give us guidance as to what they would respond to, how, and in what setting,” Dr. Edwards said.

Another panel member, Rahn K. Bailey, M.D., said that throughout his career he has been interested in issues such as differences in drug metabolism between African Americans and other patients. For example, about 40% of black patients are slow or intermediate metabolizers of many psychiatric medications, said Dr. Bailey of the department of psychiatry and human behavior, University of Texas, Houston, and chair of the NMA psychiatry and behavioral sciences section.

Because of this, black patients tend to experience more toxicity, and efficacy may be compromised. “It's not surprising to me now that many of my patients over the years have had great difficulty getting better, relapsed a lot quicker, come back to the hospital frequently, and ended up in the legal system because of clinical issues that were not addressed medically,” he said.

“In psychiatry it's as if we did all our studies on inpatients and none on outpatients, or in suburban communities rather than inner cities. The distinctions are apparent and actually affect medical decision making,” said Dr. Bailey, adding that these issues also are relevant in cardiovascular medicine, neurology, ob.gyn., and other areas of medicine.

NEW YORK — Racial disparities in access to health care will disappear only when adequate and representative samples of minorities participate in clinical trials, Winston Price, M.D., said at the annual meeting of the National Medical Association.

That disparities in delivery of health care exist is not in question. The Institute of Medicine report “Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare” revealed the extent of the problem, showing that disparities remain even after adjustment for factors such as insurance coverage and socioeconomic status.

But a widespread mistrust of the U.S. health care system among minorities—not least because of past abuses such as the Tuskegee Syphilis Study, in which blacks went untreated for many years despite the availability of effective therapy—has led to an unwillingness among African Americans to participate in the clinical trials that might directly benefit their own health.

An increasing understanding of genetic differences and racial differences in response to medications now makes it imperative that minorities be included and their needs addressed in the drug development process, said Dr. Price of the State University of New York Health Science Center, Brooklyn.

The experience with BiDil, a fixed-dose combination of isosorbide dinitrate and hydralazine approved specifically for the treatment of heart failure in black patients, shows it can be done (July 2005, p. 1).

“You had 1,050 African Americans who enrolled in the study, and the attrition rate was zero,” Dr. Price, who is also president of the NMA, said in a press briefing. “Every single one stayed with that study until completion. The drug was approved by the Food and Drug Administration on June 23, not because it was the right thing to do but because it was pure science and evidence based. All we're asking for is parity.”

Other model programs also are demonstrating that blacks can be recruited successfully, Christopher L. Edwards, Ph.D., said at the briefing. Programs that are successful tend to be well entrenched in the community; they have significant outreach and education and strong, ongoing relationships with local organizations such as churches and fraternities, Dr. Edwards said.

They do not pressure potential study participants, but rather provide information and allow patients to process the information at home and respond to the investigators when they are ready, he said.

Successful investigators are available to the community not only when recruiting; they are able to articulate the tangible benefits of participation. Dr. Edwards' program in the department of psychiatry at Duke University Medical Center, Durham, N.C., is an example.

“We make ourselves available for interviews on television, religious radio, and pop radio. In one creative marketing plan, we placed advertisements for one of our genetic studies on the side of 20 city buses, and have seen a significant number of patients responding.” he said. The overall strategy of information dissemination is to go where the patients are, and not to rely on them to come to us.

In the Duke program, the relevant stakeholders are at the table when recruiting programs are being designed. “If we are recruiting college students, we had students who sat on review panels and advisory boards to give us guidance as to what they would respond to, how, and in what setting,” Dr. Edwards said.

Another panel member, Rahn K. Bailey, M.D., said that throughout his career he has been interested in issues such as differences in drug metabolism between African Americans and other patients. For example, about 40% of black patients are slow or intermediate metabolizers of many psychiatric medications, said Dr. Bailey of the department of psychiatry and human behavior, University of Texas, Houston, and chair of the NMA psychiatry and behavioral sciences section.

Because of this, black patients tend to experience more toxicity, and efficacy may be compromised. “It's not surprising to me now that many of my patients over the years have had great difficulty getting better, relapsed a lot quicker, come back to the hospital frequently, and ended up in the legal system because of clinical issues that were not addressed medically,” he said.

“In psychiatry it's as if we did all our studies on inpatients and none on outpatients, or in suburban communities rather than inner cities. The distinctions are apparent and actually affect medical decision making,” said Dr. Bailey, adding that these issues also are relevant in cardiovascular medicine, neurology, ob.gyn., and other areas of medicine.

GLASGOW, SCOTLAND — A proprietary formulation of fumaric acid esters has proved, during decades of use in Germany, to be a useful option for some patients with severe, recalcitrant psoriasis.

Although the therapy is less than perfect—with gastrointestinal side effects, slow onset of effect, and a 10% incidence of lymphocytopenia—it can be very effective in some patients, Catherine Smith, M.D., said at the annual meeting of the British Association of Dermatologists.

Since 2002, Dr. Smith and her colleagues at the St. John's Institute of Dermatology, London, have enrolled 62 patients with severe psoriasis that did not respond to standard therapies into an open study of Fumaderm, the German formulation of fumaric acid esters.

For this group of patients, treatment duration ranged from 4 weeks to 3 years, and 24 patients discontinued treatment, generally because of lack of efficacy. Although results at 16 weeks' follow-up for the remaining patients have been mixed, with 38% showing no improvement or worsening, a small subset (8%) had substantial improvement. “Importantly, these patients with very severe disease had a greater than 50% improvement compared to baseline,” Dr. Smith said.

It generally takes 4–6 weeks before clinical effects are seen, and many patients have difficulty tolerating the drug. Gastrointestinal side effects, most commonly diarrhea, are seen in more than two-thirds. The reason for these gastrointestinal disturbances is not clear but may be related to the current formulation, which is a mixture of several different fumaric acid esters and is licensed only in Germany, Dr. Smith said. A new microtablet formulation that consists solely of dimethyl fumarate has now been through phase II studies and is expected to be licensed in the United Kingdom, she said. This formulation, currently known as BG-12, is said to be associated with fewer adverse effects.

The other most common side effect of fumarates is flushing or redness, described by some patients as tingling or skin pain. Lymphocytopenia is also fairly common but resolves on cessation of treatment. Eosinophilia is seen in 50% of patients between weeks 4 and 8 of treatment, but this has not been associated with any clinical allergic responses.

Case reports of renal failure were published during the early 1980s, but these incidents were in patients on very high dosages of the drug, and no subsequent cases have been reported, Dr. Smith said.

No notable long-term toxicities have been seen. Unlike with other systemic therapies for psoriasis, there has been no association with malignancy, she said.

While Fumaderm is more costly than some older therapies, its price tag is half that of infliximab.

Fumaric acid esters were first used in 1959 by German chemist Walter Schweckendiek, who undertook an “n of one” study on himself because his severe psoriasis had not responded to the available therapies. At the time, it was thought that psoriasis resulted from a defect in metabolism. He postulated that because fumaric acid is involved in the tricarboxylic acid cycle and is therefore fundamental to cellular respiration, exogenous administration of the drug would be beneficial. He reported that his skin began to improve within 12 hours and cleared completely in 10 days (Med. Monatschr. 1959;13:103–4).

“As a consequence, use of fumaric acid esters mushroomed in Germany, and today accounts for 66% of prescriptions for severe psoriasis in that country,” Dr. Smith said.

GLASGOW, SCOTLAND — A proprietary formulation of fumaric acid esters has proved, during decades of use in Germany, to be a useful option for some patients with severe, recalcitrant psoriasis.

Although the therapy is less than perfect—with gastrointestinal side effects, slow onset of effect, and a 10% incidence of lymphocytopenia—it can be very effective in some patients, Catherine Smith, M.D., said at the annual meeting of the British Association of Dermatologists.

Since 2002, Dr. Smith and her colleagues at the St. John's Institute of Dermatology, London, have enrolled 62 patients with severe psoriasis that did not respond to standard therapies into an open study of Fumaderm, the German formulation of fumaric acid esters.

For this group of patients, treatment duration ranged from 4 weeks to 3 years, and 24 patients discontinued treatment, generally because of lack of efficacy. Although results at 16 weeks' follow-up for the remaining patients have been mixed, with 38% showing no improvement or worsening, a small subset (8%) had substantial improvement. “Importantly, these patients with very severe disease had a greater than 50% improvement compared to baseline,” Dr. Smith said.

It generally takes 4–6 weeks before clinical effects are seen, and many patients have difficulty tolerating the drug. Gastrointestinal side effects, most commonly diarrhea, are seen in more than two-thirds. The reason for these gastrointestinal disturbances is not clear but may be related to the current formulation, which is a mixture of several different fumaric acid esters and is licensed only in Germany, Dr. Smith said. A new microtablet formulation that consists solely of dimethyl fumarate has now been through phase II studies and is expected to be licensed in the United Kingdom, she said. This formulation, currently known as BG-12, is said to be associated with fewer adverse effects.

The other most common side effect of fumarates is flushing or redness, described by some patients as tingling or skin pain. Lymphocytopenia is also fairly common but resolves on cessation of treatment. Eosinophilia is seen in 50% of patients between weeks 4 and 8 of treatment, but this has not been associated with any clinical allergic responses.

Case reports of renal failure were published during the early 1980s, but these incidents were in patients on very high dosages of the drug, and no subsequent cases have been reported, Dr. Smith said.

No notable long-term toxicities have been seen. Unlike with other systemic therapies for psoriasis, there has been no association with malignancy, she said.

While Fumaderm is more costly than some older therapies, its price tag is half that of infliximab.

Fumaric acid esters were first used in 1959 by German chemist Walter Schweckendiek, who undertook an “n of one” study on himself because his severe psoriasis had not responded to the available therapies. At the time, it was thought that psoriasis resulted from a defect in metabolism. He postulated that because fumaric acid is involved in the tricarboxylic acid cycle and is therefore fundamental to cellular respiration, exogenous administration of the drug would be beneficial. He reported that his skin began to improve within 12 hours and cleared completely in 10 days (Med. Monatschr. 1959;13:103–4).

“As a consequence, use of fumaric acid esters mushroomed in Germany, and today accounts for 66% of prescriptions for severe psoriasis in that country,” Dr. Smith said.

GLASGOW, SCOTLAND — A proprietary formulation of fumaric acid esters has proved, during decades of use in Germany, to be a useful option for some patients with severe, recalcitrant psoriasis.

Although the therapy is less than perfect—with gastrointestinal side effects, slow onset of effect, and a 10% incidence of lymphocytopenia—it can be very effective in some patients, Catherine Smith, M.D., said at the annual meeting of the British Association of Dermatologists.

Since 2002, Dr. Smith and her colleagues at the St. John's Institute of Dermatology, London, have enrolled 62 patients with severe psoriasis that did not respond to standard therapies into an open study of Fumaderm, the German formulation of fumaric acid esters.

For this group of patients, treatment duration ranged from 4 weeks to 3 years, and 24 patients discontinued treatment, generally because of lack of efficacy. Although results at 16 weeks' follow-up for the remaining patients have been mixed, with 38% showing no improvement or worsening, a small subset (8%) had substantial improvement. “Importantly, these patients with very severe disease had a greater than 50% improvement compared to baseline,” Dr. Smith said.

It generally takes 4–6 weeks before clinical effects are seen, and many patients have difficulty tolerating the drug. Gastrointestinal side effects, most commonly diarrhea, are seen in more than two-thirds. The reason for these gastrointestinal disturbances is not clear but may be related to the current formulation, which is a mixture of several different fumaric acid esters and is licensed only in Germany, Dr. Smith said. A new microtablet formulation that consists solely of dimethyl fumarate has now been through phase II studies and is expected to be licensed in the United Kingdom, she said. This formulation, currently known as BG-12, is said to be associated with fewer adverse effects.

The other most common side effect of fumarates is flushing or redness, described by some patients as tingling or skin pain. Lymphocytopenia is also fairly common but resolves on cessation of treatment. Eosinophilia is seen in 50% of patients between weeks 4 and 8 of treatment, but this has not been associated with any clinical allergic responses.

Case reports of renal failure were published during the early 1980s, but these incidents were in patients on very high dosages of the drug, and no subsequent cases have been reported, Dr. Smith said.

No notable long-term toxicities have been seen. Unlike with other systemic therapies for psoriasis, there has been no association with malignancy, she said.

While Fumaderm is more costly than some older therapies, its price tag is half that of infliximab.

Fumaric acid esters were first used in 1959 by German chemist Walter Schweckendiek, who undertook an “n of one” study on himself because his severe psoriasis had not responded to the available therapies. At the time, it was thought that psoriasis resulted from a defect in metabolism. He postulated that because fumaric acid is involved in the tricarboxylic acid cycle and is therefore fundamental to cellular respiration, exogenous administration of the drug would be beneficial. He reported that his skin began to improve within 12 hours and cleared completely in 10 days (Med. Monatschr. 1959;13:103–4).

“As a consequence, use of fumaric acid esters mushroomed in Germany, and today accounts for 66% of prescriptions for severe psoriasis in that country,” Dr. Smith said.

GLASGOW, SCOTLAND — In the first phase III trial evaluating infliximab for plaque psoriasis, substantial improvements were achieved by week 10 and sustained through week 50 in the majority of patients, Kristian Reich, M.D., reported at the annual meeting of the British Association of Dermatologists.

The 281 patients who were randomized to receive either placebo or infusions of infliximab, 5 mg/kg at week 0, 2, and 6 and every 8 weeks thereafter all had severe, recalcitrant disease. Most patients had approximately 30% skin surface involvement, one-third had concomitant arthritis, and the median psoriasis activity and severity index (PASI) score was 20, said Dr. Reich of Georg-August-University, Göttingen, Germany.

At week 10, 80% of patients receiving infliximab had achieved a PASI 75 score, indicating a 75% improvement in symptoms, and 57% had achieved a PASI 90 score. In comparison, only 2.6% and 1.3% of those in the placebo group had achieved PASI 75 and 90 scores, he said.

Moreover, 26% had a PASI 100, meaning there were no visible remaining signs of psoriasis, and 47% had a score of 0 on the Dermatology Life Quality Index, indicating that the disease was having no significant impact on social life or activities, he said.

At week 24, which was the conclusion of the placebo-controlled phase of the trial, 82% of patients had a PASI 75 response, and 58% had a PASI 90 response, compared with 3.9% and 1.3% of placebo-treated patients, respectively.

All patients subsequently entered the open phase of the trial. At week 50, intent-to-treat analysis showed that 61% of patients had a PASI 75 response, and a per-protocol analysis found that 71% maintained this level of response, he said.

Infliximab-treated patients also had significant improvements in nail psoriasis and in quality of life parameters at weeks 10 and 24.

“With [tumor necrosis factor] antagonists, of course, we have to take a close look at the safety profile,” Dr. Reich said. During the blinded phase of the trial, 6% and 3% of patients in the infliximab and placebo groups, respectively, experienced serious adverse events. These were primarily infections or infusion reactions, he said.

Analysis of the 1-year safety data has identified four serious infusion reactions, with angioedema, hypertension, and dizziness. There have been eight serious infections, four of which were abscesses, three were infections in the rectal area, and one was in the throat. There also have been three cases of lupuslike syndrome, two of which were serious, but no cases of congestive heart failure, tuberculosis, or demyelinating disorders.

Six malignancies have occurred, four squamous cell carcinomas, and two basal cell carcinomas. “With the skin cancers, it's hard to say if these were really related to infliximab. It could well be that the clearance of the psoriasis lesions allowed detection of the skin cancers, but this is an issue we have to follow closely,” he said.

“I think we can say that this is one of the most effective drugs we have in psoriasis,” he said, noting that the onset of effect is rapid, usually occurring between weeks 2 and 4 of treatment.

The study was funded by Centocor.

GLASGOW, SCOTLAND — In the first phase III trial evaluating infliximab for plaque psoriasis, substantial improvements were achieved by week 10 and sustained through week 50 in the majority of patients, Kristian Reich, M.D., reported at the annual meeting of the British Association of Dermatologists.

The 281 patients who were randomized to receive either placebo or infusions of infliximab, 5 mg/kg at week 0, 2, and 6 and every 8 weeks thereafter all had severe, recalcitrant disease. Most patients had approximately 30% skin surface involvement, one-third had concomitant arthritis, and the median psoriasis activity and severity index (PASI) score was 20, said Dr. Reich of Georg-August-University, Göttingen, Germany.

At week 10, 80% of patients receiving infliximab had achieved a PASI 75 score, indicating a 75% improvement in symptoms, and 57% had achieved a PASI 90 score. In comparison, only 2.6% and 1.3% of those in the placebo group had achieved PASI 75 and 90 scores, he said.

Moreover, 26% had a PASI 100, meaning there were no visible remaining signs of psoriasis, and 47% had a score of 0 on the Dermatology Life Quality Index, indicating that the disease was having no significant impact on social life or activities, he said.

At week 24, which was the conclusion of the placebo-controlled phase of the trial, 82% of patients had a PASI 75 response, and 58% had a PASI 90 response, compared with 3.9% and 1.3% of placebo-treated patients, respectively.

All patients subsequently entered the open phase of the trial. At week 50, intent-to-treat analysis showed that 61% of patients had a PASI 75 response, and a per-protocol analysis found that 71% maintained this level of response, he said.

Infliximab-treated patients also had significant improvements in nail psoriasis and in quality of life parameters at weeks 10 and 24.

“With [tumor necrosis factor] antagonists, of course, we have to take a close look at the safety profile,” Dr. Reich said. During the blinded phase of the trial, 6% and 3% of patients in the infliximab and placebo groups, respectively, experienced serious adverse events. These were primarily infections or infusion reactions, he said.

Analysis of the 1-year safety data has identified four serious infusion reactions, with angioedema, hypertension, and dizziness. There have been eight serious infections, four of which were abscesses, three were infections in the rectal area, and one was in the throat. There also have been three cases of lupuslike syndrome, two of which were serious, but no cases of congestive heart failure, tuberculosis, or demyelinating disorders.

Six malignancies have occurred, four squamous cell carcinomas, and two basal cell carcinomas. “With the skin cancers, it's hard to say if these were really related to infliximab. It could well be that the clearance of the psoriasis lesions allowed detection of the skin cancers, but this is an issue we have to follow closely,” he said.

“I think we can say that this is one of the most effective drugs we have in psoriasis,” he said, noting that the onset of effect is rapid, usually occurring between weeks 2 and 4 of treatment.

The study was funded by Centocor.

GLASGOW, SCOTLAND — In the first phase III trial evaluating infliximab for plaque psoriasis, substantial improvements were achieved by week 10 and sustained through week 50 in the majority of patients, Kristian Reich, M.D., reported at the annual meeting of the British Association of Dermatologists.

The 281 patients who were randomized to receive either placebo or infusions of infliximab, 5 mg/kg at week 0, 2, and 6 and every 8 weeks thereafter all had severe, recalcitrant disease. Most patients had approximately 30% skin surface involvement, one-third had concomitant arthritis, and the median psoriasis activity and severity index (PASI) score was 20, said Dr. Reich of Georg-August-University, Göttingen, Germany.

At week 10, 80% of patients receiving infliximab had achieved a PASI 75 score, indicating a 75% improvement in symptoms, and 57% had achieved a PASI 90 score. In comparison, only 2.6% and 1.3% of those in the placebo group had achieved PASI 75 and 90 scores, he said.

Moreover, 26% had a PASI 100, meaning there were no visible remaining signs of psoriasis, and 47% had a score of 0 on the Dermatology Life Quality Index, indicating that the disease was having no significant impact on social life or activities, he said.

At week 24, which was the conclusion of the placebo-controlled phase of the trial, 82% of patients had a PASI 75 response, and 58% had a PASI 90 response, compared with 3.9% and 1.3% of placebo-treated patients, respectively.

All patients subsequently entered the open phase of the trial. At week 50, intent-to-treat analysis showed that 61% of patients had a PASI 75 response, and a per-protocol analysis found that 71% maintained this level of response, he said.

Infliximab-treated patients also had significant improvements in nail psoriasis and in quality of life parameters at weeks 10 and 24.

“With [tumor necrosis factor] antagonists, of course, we have to take a close look at the safety profile,” Dr. Reich said. During the blinded phase of the trial, 6% and 3% of patients in the infliximab and placebo groups, respectively, experienced serious adverse events. These were primarily infections or infusion reactions, he said.

Analysis of the 1-year safety data has identified four serious infusion reactions, with angioedema, hypertension, and dizziness. There have been eight serious infections, four of which were abscesses, three were infections in the rectal area, and one was in the throat. There also have been three cases of lupuslike syndrome, two of which were serious, but no cases of congestive heart failure, tuberculosis, or demyelinating disorders.

Six malignancies have occurred, four squamous cell carcinomas, and two basal cell carcinomas. “With the skin cancers, it's hard to say if these were really related to infliximab. It could well be that the clearance of the psoriasis lesions allowed detection of the skin cancers, but this is an issue we have to follow closely,” he said.

“I think we can say that this is one of the most effective drugs we have in psoriasis,” he said, noting that the onset of effect is rapid, usually occurring between weeks 2 and 4 of treatment.

The study was funded by Centocor.

NEW YORK – Options are available for children with attention-deficit hyperactivity disorder who do not respond to treatment with stimulants or are troubled by side effects, but they must be chosen and used carefully, Laurence L. Greenhill, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

First the diagnosis should be reviewed, as many conditions that will not respond to stimulants can overlap or mimic ADHD. These include oppositional defiance disorder, anxiety problems, depression, occasionally bipolar disorder, and psychotic conditions.

“And don't forget substance abuse disorder, which is a pretty good neutralizer of some stimulant treatments,” said Dr. Greenhill, who is professor of clinical psychiatry at Columbia University, New York, and director of research for the pediatric psychopharmacology unit at the New York State Psychiatric Institute.

The preferred second-line drug is atomoxetine (Strattera), a nonstimulant, highly specific norepinephrine reuptake inhibitor. This is not a controlled substance, so it also is useful for parents who are uncomfortable giving their child a schedule II drug, he said.

As a 24-hour drug, atomoxetine significantly improves behavior and activities in both evening and early morning.

“The most important thing you can do for your patients is to start this drug slowly and give it twice a day when you are titrating it,” Dr. Greenhill said. Patients are much less likely to experience severe somnolence if the drug is titrated over a week, despite the fact that the labeling says upward titration to a full dose of 1.2 mg/kg per day can begin after 3 days on the initial dose of 0.5 mg/kg per day.

If the full dose is given rapidly, there is a good chance that a formerly disruptive ADHD child will fall asleep in class. “As much as that might be a refreshing change for a teacher who's been battling the noise, nothing gets a parent out of work faster than the school nurse calling and saying, 'We can't keep your son awake–come and get him.' That only has to happen once and the parents will stop the atomoxetine really fast, because they've never had this problem before,” Dr. Greenhill said.

Third-line treatments include the α-2 agonists and bupropion. Clonidine (Catapres) may be useful in treating very hyperactive or aggressive patients, but it may take several weeks to take effect and does not improve inattention symptoms. There also are risks of cardiovascular adverse effects, depression, and decreased glucose tolerance.

Guanfacine (Tenex) is a longer acting α-2 agonist that has a more favorable side effect profile than clonidine, but it has been studied only in open trials. Studies of this drug in primates suggest that it acts more on postsynaptic α-2 receptors in the prefrontal cortex than in the brainstem where clonidine works. This may prove helpful, but there's much more work to be done, Dr. Greenhill said.

Bupropion may be useful for comorbidities and is not a controlled substance, but the effect size of this drug appears to be limited. Adverse effects include irritability, insomnia, and tics.

The usual effective dose is about 300 mg/day, but seizures can result if the dose exceeds 450 mg/day. “So make sure the patient hasn't been prescribed Zyban, the other form of bupropion, for smoking cessation,” he said.

Dr. Greenhill disclosed that he has relationships with several manufacturers of drugs used to treat ADHD, including Eli Lilly & Co., the manufacturer of atomoxetine.

NEW YORK – Options are available for children with attention-deficit hyperactivity disorder who do not respond to treatment with stimulants or are troubled by side effects, but they must be chosen and used carefully, Laurence L. Greenhill, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

First the diagnosis should be reviewed, as many conditions that will not respond to stimulants can overlap or mimic ADHD. These include oppositional defiance disorder, anxiety problems, depression, occasionally bipolar disorder, and psychotic conditions.

“And don't forget substance abuse disorder, which is a pretty good neutralizer of some stimulant treatments,” said Dr. Greenhill, who is professor of clinical psychiatry at Columbia University, New York, and director of research for the pediatric psychopharmacology unit at the New York State Psychiatric Institute.

The preferred second-line drug is atomoxetine (Strattera), a nonstimulant, highly specific norepinephrine reuptake inhibitor. This is not a controlled substance, so it also is useful for parents who are uncomfortable giving their child a schedule II drug, he said.

As a 24-hour drug, atomoxetine significantly improves behavior and activities in both evening and early morning.

“The most important thing you can do for your patients is to start this drug slowly and give it twice a day when you are titrating it,” Dr. Greenhill said. Patients are much less likely to experience severe somnolence if the drug is titrated over a week, despite the fact that the labeling says upward titration to a full dose of 1.2 mg/kg per day can begin after 3 days on the initial dose of 0.5 mg/kg per day.

If the full dose is given rapidly, there is a good chance that a formerly disruptive ADHD child will fall asleep in class. “As much as that might be a refreshing change for a teacher who's been battling the noise, nothing gets a parent out of work faster than the school nurse calling and saying, 'We can't keep your son awake–come and get him.' That only has to happen once and the parents will stop the atomoxetine really fast, because they've never had this problem before,” Dr. Greenhill said.

Third-line treatments include the α-2 agonists and bupropion. Clonidine (Catapres) may be useful in treating very hyperactive or aggressive patients, but it may take several weeks to take effect and does not improve inattention symptoms. There also are risks of cardiovascular adverse effects, depression, and decreased glucose tolerance.

Guanfacine (Tenex) is a longer acting α-2 agonist that has a more favorable side effect profile than clonidine, but it has been studied only in open trials. Studies of this drug in primates suggest that it acts more on postsynaptic α-2 receptors in the prefrontal cortex than in the brainstem where clonidine works. This may prove helpful, but there's much more work to be done, Dr. Greenhill said.

Bupropion may be useful for comorbidities and is not a controlled substance, but the effect size of this drug appears to be limited. Adverse effects include irritability, insomnia, and tics.

The usual effective dose is about 300 mg/day, but seizures can result if the dose exceeds 450 mg/day. “So make sure the patient hasn't been prescribed Zyban, the other form of bupropion, for smoking cessation,” he said.

Dr. Greenhill disclosed that he has relationships with several manufacturers of drugs used to treat ADHD, including Eli Lilly & Co., the manufacturer of atomoxetine.

NEW YORK – Options are available for children with attention-deficit hyperactivity disorder who do not respond to treatment with stimulants or are troubled by side effects, but they must be chosen and used carefully, Laurence L. Greenhill, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

First the diagnosis should be reviewed, as many conditions that will not respond to stimulants can overlap or mimic ADHD. These include oppositional defiance disorder, anxiety problems, depression, occasionally bipolar disorder, and psychotic conditions.

“And don't forget substance abuse disorder, which is a pretty good neutralizer of some stimulant treatments,” said Dr. Greenhill, who is professor of clinical psychiatry at Columbia University, New York, and director of research for the pediatric psychopharmacology unit at the New York State Psychiatric Institute.

The preferred second-line drug is atomoxetine (Strattera), a nonstimulant, highly specific norepinephrine reuptake inhibitor. This is not a controlled substance, so it also is useful for parents who are uncomfortable giving their child a schedule II drug, he said.

As a 24-hour drug, atomoxetine significantly improves behavior and activities in both evening and early morning.

“The most important thing you can do for your patients is to start this drug slowly and give it twice a day when you are titrating it,” Dr. Greenhill said. Patients are much less likely to experience severe somnolence if the drug is titrated over a week, despite the fact that the labeling says upward titration to a full dose of 1.2 mg/kg per day can begin after 3 days on the initial dose of 0.5 mg/kg per day.

If the full dose is given rapidly, there is a good chance that a formerly disruptive ADHD child will fall asleep in class. “As much as that might be a refreshing change for a teacher who's been battling the noise, nothing gets a parent out of work faster than the school nurse calling and saying, 'We can't keep your son awake–come and get him.' That only has to happen once and the parents will stop the atomoxetine really fast, because they've never had this problem before,” Dr. Greenhill said.

Third-line treatments include the α-2 agonists and bupropion. Clonidine (Catapres) may be useful in treating very hyperactive or aggressive patients, but it may take several weeks to take effect and does not improve inattention symptoms. There also are risks of cardiovascular adverse effects, depression, and decreased glucose tolerance.

Guanfacine (Tenex) is a longer acting α-2 agonist that has a more favorable side effect profile than clonidine, but it has been studied only in open trials. Studies of this drug in primates suggest that it acts more on postsynaptic α-2 receptors in the prefrontal cortex than in the brainstem where clonidine works. This may prove helpful, but there's much more work to be done, Dr. Greenhill said.

Bupropion may be useful for comorbidities and is not a controlled substance, but the effect size of this drug appears to be limited. Adverse effects include irritability, insomnia, and tics.

The usual effective dose is about 300 mg/day, but seizures can result if the dose exceeds 450 mg/day. “So make sure the patient hasn't been prescribed Zyban, the other form of bupropion, for smoking cessation,” he said.

Dr. Greenhill disclosed that he has relationships with several manufacturers of drugs used to treat ADHD, including Eli Lilly & Co., the manufacturer of atomoxetine.

NEW YORK — Racial disparities in access to health care will disappear only when adequate and representative samples of minorities participate in clinical trials, Winston Price, M.D., said at the annual meeting of the National Medical Association.

That disparities in delivery of health care exist is not in question. The Institute of Medicine report “Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare” revealed the extent of the problem, showing disparities even after adjustment for factors such as insurance coverage and socioeconomic status.

But a widespread mistrust of the U.S. health care system among minorities—not least because of past abuses such as the Tuskegee Syphilis Study, in which blacks went untreated for many years despite the availability of effective therapy—has led to an unwillingness among African Americans to participate in the clinical trials that might directly benefit their own health.

An increasing understanding of genetic differences and racial differences in response to medications now makes it imperative that minorities be included and their needs addressed in the drug development process, said Dr. Price of the State University of New York Health Science Center, Brooklyn.

The experience with BiDil, a fixed-dose combination of isosorbide dinitrate and hydralazine approved specifically for the treatment of heart failure in black patients, shows it can be done.

“You had 1,050 African Americans who enrolled in the study, and the attrition rate was zero,” Dr. Price, who is also president of the NMA, said in a press briefing. “Every single one stayed with that study until completion. The drug was approved by the Food and Drug Administration on June 23, not because it was the right thing to do but because it was pure science and evidence based. All we're asking for is parity.”

Other model programs also are demonstrating that blacks can be recruited successfully, Christopher L. Edwards, Ph.D., said at the briefing.

Programs that are successful tend to be well entrenched in the community; they have significant outreach and education and strong, ongoing relationships with local organizations such as churches and fraternities, Dr. Edwards said.

They do not pressure potential study participants, but, rather, provide information and allow patients to process the information at home and respond to the investigators when they are ready, he said.

Successful investigators are available to the community not only when recruiting; they are able to articulate the tangible benefits of participation, not only for patients themselves but also for future generations.

Dr. Edwards' program in the department of psychiatry at Duke University Medical Center, Durham, N.C., is an excellent example.

“We make ourselves available for interviews on television, religious radio, and pop radio. In one creative marketing plan, we placed advertisements for one of our genetic studies on the side of 20 city buses, and have seen a significant number of patients responding,” he said.

The overall strategy of information dissemination is to go where the patients are, and not to rely on them to come to us, he said. “With the bus advertisements, the demographic we were recruiting was reliant on public transportation,” Dr. Edwards added. And the advertisements provided phone numbers, not e-mail addresses or Web sites, because the latter obviously would not be particularly helpful for a population that doesn't own computers.

In the Duke program, the relevant stakeholders are at the table when recruiting programs are being designed. “If we are recruiting college students, we had students who sat on review panels and advisory boards to give us guidance as to what they would respond to, how, and in what setting,” Dr. Edwards said.

Another panel member, Rahn K. Bailey, M.D., said that throughout his career he has been interested in issues such as differences in drug metabolism between African Americans and other patients. For example, about 40% of black patients are slow or intermediate metabolizers of many psychiatric medications, said Dr. Bailey of the department of psychiatry and human behavior, University of Texas, Houston, and chair of the NMA psychiatry and behavioral sciences section.

Because of this, black patients tend to experience more toxicity, and efficacy may be compromised, he said.

“It's not surprising to me now that many of my patients over the years have had great difficulty getting better, relapsed a lot quicker, come back to the hospital frequently, and ended up in the legal system because of clinical issues that were not addressed medically,” Dr. Bailey said.

“In psychiatry it's as if we did all our studies on inpatients and none on outpatients, or in suburban communities rather than inner cities. The distinctions are apparent and actually affect medical decision making, he said, adding that these issues also are relevant in cardiovascular medicine, neurology, ob.gyn., and other areas of medicine.

Audience member William Lawson, M.D., brought up the work of Surgeon General David Satcher, M.D., Ph.D., in his 1999 report “Mental Health: A Report of the Surgeon General.” One of the points made in this report was that virtually all psychiatric studies done in the United States included primarily white males, so almost all the available psychiatric drugs had less than 1% African American participation, said Dr. Lawson, chair of psychiatry, Howard University, Washington.

“And the consequences have been awful. For example, once the second-generation antipsychotic medications came on the market it became clear that the risk of obesity, diabetes, and metabolic syndrome was much more of a problem for African Americans and Hispanics than for whites. We don't want to improve the mental health of our patients at the expense of giving them complications that can be lethal,” Dr. Lawson said.

NEW YORK — Racial disparities in access to health care will disappear only when adequate and representative samples of minorities participate in clinical trials, Winston Price, M.D., said at the annual meeting of the National Medical Association.

That disparities in delivery of health care exist is not in question. The Institute of Medicine report “Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare” revealed the extent of the problem, showing disparities even after adjustment for factors such as insurance coverage and socioeconomic status.

But a widespread mistrust of the U.S. health care system among minorities—not least because of past abuses such as the Tuskegee Syphilis Study, in which blacks went untreated for many years despite the availability of effective therapy—has led to an unwillingness among African Americans to participate in the clinical trials that might directly benefit their own health.

An increasing understanding of genetic differences and racial differences in response to medications now makes it imperative that minorities be included and their needs addressed in the drug development process, said Dr. Price of the State University of New York Health Science Center, Brooklyn.

The experience with BiDil, a fixed-dose combination of isosorbide dinitrate and hydralazine approved specifically for the treatment of heart failure in black patients, shows it can be done.

“You had 1,050 African Americans who enrolled in the study, and the attrition rate was zero,” Dr. Price, who is also president of the NMA, said in a press briefing. “Every single one stayed with that study until completion. The drug was approved by the Food and Drug Administration on June 23, not because it was the right thing to do but because it was pure science and evidence based. All we're asking for is parity.”

Other model programs also are demonstrating that blacks can be recruited successfully, Christopher L. Edwards, Ph.D., said at the briefing.

Programs that are successful tend to be well entrenched in the community; they have significant outreach and education and strong, ongoing relationships with local organizations such as churches and fraternities, Dr. Edwards said.

They do not pressure potential study participants, but, rather, provide information and allow patients to process the information at home and respond to the investigators when they are ready, he said.

Successful investigators are available to the community not only when recruiting; they are able to articulate the tangible benefits of participation, not only for patients themselves but also for future generations.

Dr. Edwards' program in the department of psychiatry at Duke University Medical Center, Durham, N.C., is an excellent example.

“We make ourselves available for interviews on television, religious radio, and pop radio. In one creative marketing plan, we placed advertisements for one of our genetic studies on the side of 20 city buses, and have seen a significant number of patients responding,” he said.

The overall strategy of information dissemination is to go where the patients are, and not to rely on them to come to us, he said. “With the bus advertisements, the demographic we were recruiting was reliant on public transportation,” Dr. Edwards added. And the advertisements provided phone numbers, not e-mail addresses or Web sites, because the latter obviously would not be particularly helpful for a population that doesn't own computers.

In the Duke program, the relevant stakeholders are at the table when recruiting programs are being designed. “If we are recruiting college students, we had students who sat on review panels and advisory boards to give us guidance as to what they would respond to, how, and in what setting,” Dr. Edwards said.

Another panel member, Rahn K. Bailey, M.D., said that throughout his career he has been interested in issues such as differences in drug metabolism between African Americans and other patients. For example, about 40% of black patients are slow or intermediate metabolizers of many psychiatric medications, said Dr. Bailey of the department of psychiatry and human behavior, University of Texas, Houston, and chair of the NMA psychiatry and behavioral sciences section.

Because of this, black patients tend to experience more toxicity, and efficacy may be compromised, he said.

“It's not surprising to me now that many of my patients over the years have had great difficulty getting better, relapsed a lot quicker, come back to the hospital frequently, and ended up in the legal system because of clinical issues that were not addressed medically,” Dr. Bailey said.

“In psychiatry it's as if we did all our studies on inpatients and none on outpatients, or in suburban communities rather than inner cities. The distinctions are apparent and actually affect medical decision making, he said, adding that these issues also are relevant in cardiovascular medicine, neurology, ob.gyn., and other areas of medicine.

Audience member William Lawson, M.D., brought up the work of Surgeon General David Satcher, M.D., Ph.D., in his 1999 report “Mental Health: A Report of the Surgeon General.” One of the points made in this report was that virtually all psychiatric studies done in the United States included primarily white males, so almost all the available psychiatric drugs had less than 1% African American participation, said Dr. Lawson, chair of psychiatry, Howard University, Washington.

“And the consequences have been awful. For example, once the second-generation antipsychotic medications came on the market it became clear that the risk of obesity, diabetes, and metabolic syndrome was much more of a problem for African Americans and Hispanics than for whites. We don't want to improve the mental health of our patients at the expense of giving them complications that can be lethal,” Dr. Lawson said.

NEW YORK — Racial disparities in access to health care will disappear only when adequate and representative samples of minorities participate in clinical trials, Winston Price, M.D., said at the annual meeting of the National Medical Association.

That disparities in delivery of health care exist is not in question. The Institute of Medicine report “Unequal Treatment: Confronting Racial and Ethnic Disparities in Healthcare” revealed the extent of the problem, showing disparities even after adjustment for factors such as insurance coverage and socioeconomic status.

But a widespread mistrust of the U.S. health care system among minorities—not least because of past abuses such as the Tuskegee Syphilis Study, in which blacks went untreated for many years despite the availability of effective therapy—has led to an unwillingness among African Americans to participate in the clinical trials that might directly benefit their own health.

An increasing understanding of genetic differences and racial differences in response to medications now makes it imperative that minorities be included and their needs addressed in the drug development process, said Dr. Price of the State University of New York Health Science Center, Brooklyn.

The experience with BiDil, a fixed-dose combination of isosorbide dinitrate and hydralazine approved specifically for the treatment of heart failure in black patients, shows it can be done.

“You had 1,050 African Americans who enrolled in the study, and the attrition rate was zero,” Dr. Price, who is also president of the NMA, said in a press briefing. “Every single one stayed with that study until completion. The drug was approved by the Food and Drug Administration on June 23, not because it was the right thing to do but because it was pure science and evidence based. All we're asking for is parity.”

Other model programs also are demonstrating that blacks can be recruited successfully, Christopher L. Edwards, Ph.D., said at the briefing.

Programs that are successful tend to be well entrenched in the community; they have significant outreach and education and strong, ongoing relationships with local organizations such as churches and fraternities, Dr. Edwards said.

They do not pressure potential study participants, but, rather, provide information and allow patients to process the information at home and respond to the investigators when they are ready, he said.

Successful investigators are available to the community not only when recruiting; they are able to articulate the tangible benefits of participation, not only for patients themselves but also for future generations.

Dr. Edwards' program in the department of psychiatry at Duke University Medical Center, Durham, N.C., is an excellent example.

“We make ourselves available for interviews on television, religious radio, and pop radio. In one creative marketing plan, we placed advertisements for one of our genetic studies on the side of 20 city buses, and have seen a significant number of patients responding,” he said.

The overall strategy of information dissemination is to go where the patients are, and not to rely on them to come to us, he said. “With the bus advertisements, the demographic we were recruiting was reliant on public transportation,” Dr. Edwards added. And the advertisements provided phone numbers, not e-mail addresses or Web sites, because the latter obviously would not be particularly helpful for a population that doesn't own computers.

In the Duke program, the relevant stakeholders are at the table when recruiting programs are being designed. “If we are recruiting college students, we had students who sat on review panels and advisory boards to give us guidance as to what they would respond to, how, and in what setting,” Dr. Edwards said.

Another panel member, Rahn K. Bailey, M.D., said that throughout his career he has been interested in issues such as differences in drug metabolism between African Americans and other patients. For example, about 40% of black patients are slow or intermediate metabolizers of many psychiatric medications, said Dr. Bailey of the department of psychiatry and human behavior, University of Texas, Houston, and chair of the NMA psychiatry and behavioral sciences section.

Because of this, black patients tend to experience more toxicity, and efficacy may be compromised, he said.

“It's not surprising to me now that many of my patients over the years have had great difficulty getting better, relapsed a lot quicker, come back to the hospital frequently, and ended up in the legal system because of clinical issues that were not addressed medically,” Dr. Bailey said.

“In psychiatry it's as if we did all our studies on inpatients and none on outpatients, or in suburban communities rather than inner cities. The distinctions are apparent and actually affect medical decision making, he said, adding that these issues also are relevant in cardiovascular medicine, neurology, ob.gyn., and other areas of medicine.

Audience member William Lawson, M.D., brought up the work of Surgeon General David Satcher, M.D., Ph.D., in his 1999 report “Mental Health: A Report of the Surgeon General.” One of the points made in this report was that virtually all psychiatric studies done in the United States included primarily white males, so almost all the available psychiatric drugs had less than 1% African American participation, said Dr. Lawson, chair of psychiatry, Howard University, Washington.

“And the consequences have been awful. For example, once the second-generation antipsychotic medications came on the market it became clear that the risk of obesity, diabetes, and metabolic syndrome was much more of a problem for African Americans and Hispanics than for whites. We don't want to improve the mental health of our patients at the expense of giving them complications that can be lethal,” Dr. Lawson said.

LONDON — Patients with systemic lupus erythematosus who don't get the influenza vaccine risk getting pneumonia or bronchitis—or making their underlying disease worse, a new study suggested.

Influenza vaccination for patients with autoimmune disease has long been a subject of contention. For lupus patients, the concerns have been that the vaccine could make their disease worse and that antibody responses might be inadequate. There also have been reports of lupus flares following pneumococcal immunization and a report of a patient who developed diffuse proliferative glomerulonephritis after receiving the vaccine during a lupus flare.

But the safety and efficacy of the vaccine were confirmed in a study presented in a poster session at the Sixth European Lupus Meeting. The study included 69 patients with stable disease and whose prednisone dose was 10 mg/day or less. Of these patients, 13 were in remission and given the vaccine (Vaxigrip); the other 56 did not receive the vaccine. The patients, aged 19–73 years, were followed throughout the next year for disease activity and respiratory tract infections.

Among patients who received the vaccine, 2 (15.4%) developed acute bronchitis that required antibiotic treatment, as did 17 (30.4%) of those who had not been immunized, said Ljudmila Stojanovich, M.D., of Bezhanijska Kosa University Medical Center, Belgrade, Serbia and Montenegro.

None of the vaccinated patients developed pneumonia or showed worsening of their SLE symptoms. Among the unvaccinated patients, one developed pneumonia, and two experienced worsening of their SLE symptoms following respiratory tract infections, she said at the meeting, sponsored by the British Society for Rheumatology.

Other infections, including herpes zoster and infections caused by Staphylococcus aureus, also occurred significantly more often in unvaccinated patients, and particularly in patients older than 30 years. The U.S. Advisory Committee on Immunization Practices recommends influenza vaccination for patients 2–64 years old who are at increased risk for pneumococcal infection due to chronic illnesses.

LONDON — Patients with systemic lupus erythematosus who don't get the influenza vaccine risk getting pneumonia or bronchitis—or making their underlying disease worse, a new study suggested.

Influenza vaccination for patients with autoimmune disease has long been a subject of contention. For lupus patients, the concerns have been that the vaccine could make their disease worse and that antibody responses might be inadequate. There also have been reports of lupus flares following pneumococcal immunization and a report of a patient who developed diffuse proliferative glomerulonephritis after receiving the vaccine during a lupus flare.

But the safety and efficacy of the vaccine were confirmed in a study presented in a poster session at the Sixth European Lupus Meeting. The study included 69 patients with stable disease and whose prednisone dose was 10 mg/day or less. Of these patients, 13 were in remission and given the vaccine (Vaxigrip); the other 56 did not receive the vaccine. The patients, aged 19–73 years, were followed throughout the next year for disease activity and respiratory tract infections.

Among patients who received the vaccine, 2 (15.4%) developed acute bronchitis that required antibiotic treatment, as did 17 (30.4%) of those who had not been immunized, said Ljudmila Stojanovich, M.D., of Bezhanijska Kosa University Medical Center, Belgrade, Serbia and Montenegro.

None of the vaccinated patients developed pneumonia or showed worsening of their SLE symptoms. Among the unvaccinated patients, one developed pneumonia, and two experienced worsening of their SLE symptoms following respiratory tract infections, she said at the meeting, sponsored by the British Society for Rheumatology.

Other infections, including herpes zoster and infections caused by Staphylococcus aureus, also occurred significantly more often in unvaccinated patients, and particularly in patients older than 30 years. The U.S. Advisory Committee on Immunization Practices recommends influenza vaccination for patients 2–64 years old who are at increased risk for pneumococcal infection due to chronic illnesses.

LONDON — Patients with systemic lupus erythematosus who don't get the influenza vaccine risk getting pneumonia or bronchitis—or making their underlying disease worse, a new study suggested.

Influenza vaccination for patients with autoimmune disease has long been a subject of contention. For lupus patients, the concerns have been that the vaccine could make their disease worse and that antibody responses might be inadequate. There also have been reports of lupus flares following pneumococcal immunization and a report of a patient who developed diffuse proliferative glomerulonephritis after receiving the vaccine during a lupus flare.

But the safety and efficacy of the vaccine were confirmed in a study presented in a poster session at the Sixth European Lupus Meeting. The study included 69 patients with stable disease and whose prednisone dose was 10 mg/day or less. Of these patients, 13 were in remission and given the vaccine (Vaxigrip); the other 56 did not receive the vaccine. The patients, aged 19–73 years, were followed throughout the next year for disease activity and respiratory tract infections.

Among patients who received the vaccine, 2 (15.4%) developed acute bronchitis that required antibiotic treatment, as did 17 (30.4%) of those who had not been immunized, said Ljudmila Stojanovich, M.D., of Bezhanijska Kosa University Medical Center, Belgrade, Serbia and Montenegro.

None of the vaccinated patients developed pneumonia or showed worsening of their SLE symptoms. Among the unvaccinated patients, one developed pneumonia, and two experienced worsening of their SLE symptoms following respiratory tract infections, she said at the meeting, sponsored by the British Society for Rheumatology.

Other infections, including herpes zoster and infections caused by Staphylococcus aureus, also occurred significantly more often in unvaccinated patients, and particularly in patients older than 30 years. The U.S. Advisory Committee on Immunization Practices recommends influenza vaccination for patients 2–64 years old who are at increased risk for pneumococcal infection due to chronic illnesses.

VIENNA — Cigarette smoking confers a clear and significant risk of worse clinical outcomes in patients with rheumatoid arthritis and adds to the overall health care burden because of greater therapeutic requirements—including the need for expensive biologic drugs.

Studies have documented an association between smoking and rheumatoid arthritis (RA), but the linkage with specific clinical manifestations has remained unclear. Data from the Consortium of Rheumatology Researchers of North America (CORRONA) now have confirmed that smokers have increased tender and swollen joint counts compared with nonsmokers, as well as an elevated incidence of subcutaneous nodules, Lori A. Lavalle, M.D., said at the annual European congress of rheumatology.

The CORRONA database includes 8,228 patients, drawn from 63 sites across the United States. These patients have been followed since October 2001, with data collection being done approximately every 5 months. A total of 3,266 reported ever having smoked and 1,082 are current smokers, said Dr. Lavalle, who was affiliated with the Albany (N.Y.) Medical College at the time of the presentation.

Among patients who reported ever having smoked, mean tender and swollen joint counts were 4.08 and 4.60, respectively, compared with 3.59 and 4.22 among nonsmokers. This difference was statistically significant, she said.

Other variables—including rheumatoid factor (RF) positivity (76% smokers vs. 69% nonsmokers) and health assessment questionnaire (HAQ) scores (0.53 smokers vs. 0.48 nonsmokers)—also were worse among patients who had ever smoked.

When previous smokers were compared with those who had never smoked, significant differences were seen in HAQ scores, although not in other variables.

The analysis also revealed that a greater percentage of smokers (43%) than nonsmokers (41%) were on biologic agents. In addition, 32% of smokers and 24% of nonsmokers had subcutaneous nodules.

A second study presented in a poster session further highlighted the increased requirement for drug therapy among RA patients who smoke, and particularly among those who are RF positive. This study included 856 patients recruited from 60 German rheumatology clinics, 198 (23.1%) of whom were smokers.

By 6 months, the proportion of patients requiring disease-modifying antirheumatic drugs (DMARDs) was greater among RF-positive smokers than among RF-positive nonsmokers, Gisela Westhoff reported at the meeting, which was sponsored by the European League Against Rheumatism.

This difference increased throughout the 3-year course of the study, and similar differences were seen among RF-negative smokers and nonsmokers. (See table.)

With regard to drug therapy, RF-positive smokers had taken 2.1 different DMARDs by the end of the 3-year study, whereas RF-positive nonsmokers had taken only 1.7, said Ms. Westhoff of the German Rheumatism Research Center, Berlin.

Significantly more smokers were classified as “problematic cases” by their physicians because of inadequate response to treatment, she said.

This ongoing inception cohort study is being funded by the German Federal Minister of Research through the Competence Network Rheumatology.

VIENNA — Cigarette smoking confers a clear and significant risk of worse clinical outcomes in patients with rheumatoid arthritis and adds to the overall health care burden because of greater therapeutic requirements—including the need for expensive biologic drugs.

Studies have documented an association between smoking and rheumatoid arthritis (RA), but the linkage with specific clinical manifestations has remained unclear. Data from the Consortium of Rheumatology Researchers of North America (CORRONA) now have confirmed that smokers have increased tender and swollen joint counts compared with nonsmokers, as well as an elevated incidence of subcutaneous nodules, Lori A. Lavalle, M.D., said at the annual European congress of rheumatology.

The CORRONA database includes 8,228 patients, drawn from 63 sites across the United States. These patients have been followed since October 2001, with data collection being done approximately every 5 months. A total of 3,266 reported ever having smoked and 1,082 are current smokers, said Dr. Lavalle, who was affiliated with the Albany (N.Y.) Medical College at the time of the presentation.

Among patients who reported ever having smoked, mean tender and swollen joint counts were 4.08 and 4.60, respectively, compared with 3.59 and 4.22 among nonsmokers. This difference was statistically significant, she said.

Other variables—including rheumatoid factor (RF) positivity (76% smokers vs. 69% nonsmokers) and health assessment questionnaire (HAQ) scores (0.53 smokers vs. 0.48 nonsmokers)—also were worse among patients who had ever smoked.

When previous smokers were compared with those who had never smoked, significant differences were seen in HAQ scores, although not in other variables.

The analysis also revealed that a greater percentage of smokers (43%) than nonsmokers (41%) were on biologic agents. In addition, 32% of smokers and 24% of nonsmokers had subcutaneous nodules.

A second study presented in a poster session further highlighted the increased requirement for drug therapy among RA patients who smoke, and particularly among those who are RF positive. This study included 856 patients recruited from 60 German rheumatology clinics, 198 (23.1%) of whom were smokers.

By 6 months, the proportion of patients requiring disease-modifying antirheumatic drugs (DMARDs) was greater among RF-positive smokers than among RF-positive nonsmokers, Gisela Westhoff reported at the meeting, which was sponsored by the European League Against Rheumatism.

This difference increased throughout the 3-year course of the study, and similar differences were seen among RF-negative smokers and nonsmokers. (See table.)

With regard to drug therapy, RF-positive smokers had taken 2.1 different DMARDs by the end of the 3-year study, whereas RF-positive nonsmokers had taken only 1.7, said Ms. Westhoff of the German Rheumatism Research Center, Berlin.

Significantly more smokers were classified as “problematic cases” by their physicians because of inadequate response to treatment, she said.

This ongoing inception cohort study is being funded by the German Federal Minister of Research through the Competence Network Rheumatology.

VIENNA — Cigarette smoking confers a clear and significant risk of worse clinical outcomes in patients with rheumatoid arthritis and adds to the overall health care burden because of greater therapeutic requirements—including the need for expensive biologic drugs.

Studies have documented an association between smoking and rheumatoid arthritis (RA), but the linkage with specific clinical manifestations has remained unclear. Data from the Consortium of Rheumatology Researchers of North America (CORRONA) now have confirmed that smokers have increased tender and swollen joint counts compared with nonsmokers, as well as an elevated incidence of subcutaneous nodules, Lori A. Lavalle, M.D., said at the annual European congress of rheumatology.

The CORRONA database includes 8,228 patients, drawn from 63 sites across the United States. These patients have been followed since October 2001, with data collection being done approximately every 5 months. A total of 3,266 reported ever having smoked and 1,082 are current smokers, said Dr. Lavalle, who was affiliated with the Albany (N.Y.) Medical College at the time of the presentation.

Among patients who reported ever having smoked, mean tender and swollen joint counts were 4.08 and 4.60, respectively, compared with 3.59 and 4.22 among nonsmokers. This difference was statistically significant, she said.

Other variables—including rheumatoid factor (RF) positivity (76% smokers vs. 69% nonsmokers) and health assessment questionnaire (HAQ) scores (0.53 smokers vs. 0.48 nonsmokers)—also were worse among patients who had ever smoked.

When previous smokers were compared with those who had never smoked, significant differences were seen in HAQ scores, although not in other variables.

The analysis also revealed that a greater percentage of smokers (43%) than nonsmokers (41%) were on biologic agents. In addition, 32% of smokers and 24% of nonsmokers had subcutaneous nodules.

A second study presented in a poster session further highlighted the increased requirement for drug therapy among RA patients who smoke, and particularly among those who are RF positive. This study included 856 patients recruited from 60 German rheumatology clinics, 198 (23.1%) of whom were smokers.

By 6 months, the proportion of patients requiring disease-modifying antirheumatic drugs (DMARDs) was greater among RF-positive smokers than among RF-positive nonsmokers, Gisela Westhoff reported at the meeting, which was sponsored by the European League Against Rheumatism.

This difference increased throughout the 3-year course of the study, and similar differences were seen among RF-negative smokers and nonsmokers. (See table.)

With regard to drug therapy, RF-positive smokers had taken 2.1 different DMARDs by the end of the 3-year study, whereas RF-positive nonsmokers had taken only 1.7, said Ms. Westhoff of the German Rheumatism Research Center, Berlin.

Significantly more smokers were classified as “problematic cases” by their physicians because of inadequate response to treatment, she said.

This ongoing inception cohort study is being funded by the German Federal Minister of Research through the Competence Network Rheumatology.

LONDON — The incidence of coronary heart disease among young women with systemic lupus erythematosus is “startlingly” worrisome, Ian Bruce, M.D., said at the Sixth European Lupus Meeting.

Studies have shown that the annual incidence of ischemic heart disease in lupus patients is 1.3%–1.5%. In comparison, the incidence among those with newly diagnosed type 2 diabetes and among those who have had a first myocardial infarction is 2%–2.2% per annum. “This latter number may be higher, but you have to remember that these are men in their mid- to late 50s, while the lupus patients in these studies are women whose average age is 35–37,” said Dr. Bruce, of the University of Manchester (England).

The prevalence of myocardial infarction or angina in lupus cohorts ranges from 7% to 10%, depending on patient age and duration of follow-up, he said.

Moreover, as survival improves, the prevalence of the disease increases, as does the proportion of lupus patients who are older and at even greater risk for cardiovascular disease, he said.

Some epidemiologic work has suggested that the peak age of onset also is increasing and now occurs between the fifth and seventh decades. Damage accrues more quickly among patients who are older at onset, he added.

Atherosclerosis also occurs much earlier in women with lupus than in healthy women. “In women younger than 45 in the general population, you virtually do not see plaque, whereas women with lupus are beginning to acquire plaque at that early age,” Dr. Bruce said.

Classic risk factors clearly are implicated in the premature atherosclerosis and coronary heart disease seen in lupus. There is a much higher prevalence of hypertension, diabetes, and renal impairment, and lupus patients typically have other risk factors such as higher levels of LDL cholesterol and triglycerides (Arthritis Rheum. 2003;48:3159–67).

And these risk factors do have an impact. “In a cohort study, we stratified patients according to their total cholesterol levels and found that among those with persistently elevated cholesterol, 24% developed a cardiac event during 12 years of follow-up, compared with 3% whose cholesterol level was normal or varied only slightly with disease flares,” Dr. Bruce said at the meeting, sponsored by the British Society for Rheumatology.

But classic risk factors do not tell the whole story. (See box.) In the general population, risk for a cardiac event increases as risk factors accumulate. “Lupus patients, however, seem to be set at an intrinsically higher baseline, and the accumulation of risk factors has an even more devastating effect,” he said.

A great need exists for properly conducted clinical trials of potential interventions for these patients. “We need to see if what we think will work actually does work and what the magnitude of risk reduction is with a particular intervention,” he said.

Statins are an example. “Everywhere they have been used so far, they have been associated with a reduction in risk of coronary disease events by about 30%. You could assume that also might be the case in lupus, but that could be a dangerous assumption, because these drugs might not be as well tolerated by lupus patients,” Dr. Bruce said.

Mediators and Markers: Look for Clues

As the severity of atherosclerosis and heart disease in systemic lupus erythematosus (SLE) becomes clearer, so do possible mediators and markers. A series of posters presented at the meeting by researchers from the Karolinska Institute, Stockholm, explored potential contributing factors:

▸ LDL cholesterol. Increased LDL-cholesterol oxidation contributes to lupus-related cardiovascular disease, reported Anna Cederholm, M.D. She presented data on 26 women with lupus plus cardiovascular disease, 26 women with lupus but no clinical manifestations of cardiovascular disease, and 26 normal controls.

Circulating levels of oxidized LDL cholesterol were increased in both lupus groups, as was platelet-activating factor acetylhydrolase (PAF-AH). Levels of oxidized LDL cholesterol and PAF-AH also were significantly higher in the lupus patients with cardiovascular disease than in those with lupus and no heart disease. Because PAF-AH binds to LDL cholesterol, it also may contribute to atherogenesis, Dr. Cederholm said.

▸ Anti-HDL-cholesterol antibodies. SLE-related dyslipidemia showed a surprising pattern in a study of women with a history of cardiovascular disease, reported J. Su, M.D. Large, rather than small, LDL- and HDL- cholesterol particles characterized the dyslipidemia profile. This was not an expected atherogenic lipid profile.

Antibodies against apolipoprotein A1 in HDL cholesterol also were elevated and were associated with the presence of tumor necrosis factor. Whether these anti-apo A1 antibodies play a pathogenic role—for example, by inhibiting the anti-inflammatory properties of HDL—is under investigation, Dr. Su said.

▸ Homocysteine. Hyperhomocysteinemia in patients with lupus correlates with markers of inflammatory activity and is a risk factor for cardiovascular disease, said Elisabet Svenungsson, M.D. In fasting blood samples obtained from a cohort of 208 patients, homocysteine levels were associated with acute phase reactants including C-reactive protein, serum amyloid A protein, fibrinogen, and complement.

Hyperhomocysteinemia also correlated with the presence of arterial disease and nephritis. “It may cause endothelial activation and damage and thus adds to the inflammatory burden that we believe renders SLE patients highly susceptible to cardiovascular disease,” she said.

LONDON — The incidence of coronary heart disease among young women with systemic lupus erythematosus is “startlingly” worrisome, Ian Bruce, M.D., said at the Sixth European Lupus Meeting.

Studies have shown that the annual incidence of ischemic heart disease in lupus patients is 1.3%–1.5%. In comparison, the incidence among those with newly diagnosed type 2 diabetes and among those who have had a first myocardial infarction is 2%–2.2% per annum. “This latter number may be higher, but you have to remember that these are men in their mid- to late 50s, while the lupus patients in these studies are women whose average age is 35–37,” said Dr. Bruce, of the University of Manchester (England).

The prevalence of myocardial infarction or angina in lupus cohorts ranges from 7% to 10%, depending on patient age and duration of follow-up, he said.

Moreover, as survival improves, the prevalence of the disease increases, as does the proportion of lupus patients who are older and at even greater risk for cardiovascular disease, he said.

Some epidemiologic work has suggested that the peak age of onset also is increasing and now occurs between the fifth and seventh decades. Damage accrues more quickly among patients who are older at onset, he added.

Atherosclerosis also occurs much earlier in women with lupus than in healthy women. “In women younger than 45 in the general population, you virtually do not see plaque, whereas women with lupus are beginning to acquire plaque at that early age,” Dr. Bruce said.

Classic risk factors clearly are implicated in the premature atherosclerosis and coronary heart disease seen in lupus. There is a much higher prevalence of hypertension, diabetes, and renal impairment, and lupus patients typically have other risk factors such as higher levels of LDL cholesterol and triglycerides (Arthritis Rheum. 2003;48:3159–67).

And these risk factors do have an impact. “In a cohort study, we stratified patients according to their total cholesterol levels and found that among those with persistently elevated cholesterol, 24% developed a cardiac event during 12 years of follow-up, compared with 3% whose cholesterol level was normal or varied only slightly with disease flares,” Dr. Bruce said at the meeting, sponsored by the British Society for Rheumatology.

But classic risk factors do not tell the whole story. (See box.) In the general population, risk for a cardiac event increases as risk factors accumulate. “Lupus patients, however, seem to be set at an intrinsically higher baseline, and the accumulation of risk factors has an even more devastating effect,” he said.

A great need exists for properly conducted clinical trials of potential interventions for these patients. “We need to see if what we think will work actually does work and what the magnitude of risk reduction is with a particular intervention,” he said.

Statins are an example. “Everywhere they have been used so far, they have been associated with a reduction in risk of coronary disease events by about 30%. You could assume that also might be the case in lupus, but that could be a dangerous assumption, because these drugs might not be as well tolerated by lupus patients,” Dr. Bruce said.

Mediators and Markers: Look for Clues

As the severity of atherosclerosis and heart disease in systemic lupus erythematosus (SLE) becomes clearer, so do possible mediators and markers. A series of posters presented at the meeting by researchers from the Karolinska Institute, Stockholm, explored potential contributing factors:

▸ LDL cholesterol. Increased LDL-cholesterol oxidation contributes to lupus-related cardiovascular disease, reported Anna Cederholm, M.D. She presented data on 26 women with lupus plus cardiovascular disease, 26 women with lupus but no clinical manifestations of cardiovascular disease, and 26 normal controls.

Circulating levels of oxidized LDL cholesterol were increased in both lupus groups, as was platelet-activating factor acetylhydrolase (PAF-AH). Levels of oxidized LDL cholesterol and PAF-AH also were significantly higher in the lupus patients with cardiovascular disease than in those with lupus and no heart disease. Because PAF-AH binds to LDL cholesterol, it also may contribute to atherogenesis, Dr. Cederholm said.

▸ Anti-HDL-cholesterol antibodies. SLE-related dyslipidemia showed a surprising pattern in a study of women with a history of cardiovascular disease, reported J. Su, M.D. Large, rather than small, LDL- and HDL- cholesterol particles characterized the dyslipidemia profile. This was not an expected atherogenic lipid profile.

Antibodies against apolipoprotein A1 in HDL cholesterol also were elevated and were associated with the presence of tumor necrosis factor. Whether these anti-apo A1 antibodies play a pathogenic role—for example, by inhibiting the anti-inflammatory properties of HDL—is under investigation, Dr. Su said.

▸ Homocysteine. Hyperhomocysteinemia in patients with lupus correlates with markers of inflammatory activity and is a risk factor for cardiovascular disease, said Elisabet Svenungsson, M.D. In fasting blood samples obtained from a cohort of 208 patients, homocysteine levels were associated with acute phase reactants including C-reactive protein, serum amyloid A protein, fibrinogen, and complement.

Hyperhomocysteinemia also correlated with the presence of arterial disease and nephritis. “It may cause endothelial activation and damage and thus adds to the inflammatory burden that we believe renders SLE patients highly susceptible to cardiovascular disease,” she said.

LONDON — The incidence of coronary heart disease among young women with systemic lupus erythematosus is “startlingly” worrisome, Ian Bruce, M.D., said at the Sixth European Lupus Meeting.

Studies have shown that the annual incidence of ischemic heart disease in lupus patients is 1.3%–1.5%. In comparison, the incidence among those with newly diagnosed type 2 diabetes and among those who have had a first myocardial infarction is 2%–2.2% per annum. “This latter number may be higher, but you have to remember that these are men in their mid- to late 50s, while the lupus patients in these studies are women whose average age is 35–37,” said Dr. Bruce, of the University of Manchester (England).

The prevalence of myocardial infarction or angina in lupus cohorts ranges from 7% to 10%, depending on patient age and duration of follow-up, he said.

Moreover, as survival improves, the prevalence of the disease increases, as does the proportion of lupus patients who are older and at even greater risk for cardiovascular disease, he said.

Some epidemiologic work has suggested that the peak age of onset also is increasing and now occurs between the fifth and seventh decades. Damage accrues more quickly among patients who are older at onset, he added.

Atherosclerosis also occurs much earlier in women with lupus than in healthy women. “In women younger than 45 in the general population, you virtually do not see plaque, whereas women with lupus are beginning to acquire plaque at that early age,” Dr. Bruce said.

Classic risk factors clearly are implicated in the premature atherosclerosis and coronary heart disease seen in lupus. There is a much higher prevalence of hypertension, diabetes, and renal impairment, and lupus patients typically have other risk factors such as higher levels of LDL cholesterol and triglycerides (Arthritis Rheum. 2003;48:3159–67).

And these risk factors do have an impact. “In a cohort study, we stratified patients according to their total cholesterol levels and found that among those with persistently elevated cholesterol, 24% developed a cardiac event during 12 years of follow-up, compared with 3% whose cholesterol level was normal or varied only slightly with disease flares,” Dr. Bruce said at the meeting, sponsored by the British Society for Rheumatology.

But classic risk factors do not tell the whole story. (See box.) In the general population, risk for a cardiac event increases as risk factors accumulate. “Lupus patients, however, seem to be set at an intrinsically higher baseline, and the accumulation of risk factors has an even more devastating effect,” he said.

A great need exists for properly conducted clinical trials of potential interventions for these patients. “We need to see if what we think will work actually does work and what the magnitude of risk reduction is with a particular intervention,” he said.

Statins are an example. “Everywhere they have been used so far, they have been associated with a reduction in risk of coronary disease events by about 30%. You could assume that also might be the case in lupus, but that could be a dangerous assumption, because these drugs might not be as well tolerated by lupus patients,” Dr. Bruce said.

Mediators and Markers: Look for Clues

As the severity of atherosclerosis and heart disease in systemic lupus erythematosus (SLE) becomes clearer, so do possible mediators and markers. A series of posters presented at the meeting by researchers from the Karolinska Institute, Stockholm, explored potential contributing factors:

▸ LDL cholesterol. Increased LDL-cholesterol oxidation contributes to lupus-related cardiovascular disease, reported Anna Cederholm, M.D. She presented data on 26 women with lupus plus cardiovascular disease, 26 women with lupus but no clinical manifestations of cardiovascular disease, and 26 normal controls.

Circulating levels of oxidized LDL cholesterol were increased in both lupus groups, as was platelet-activating factor acetylhydrolase (PAF-AH). Levels of oxidized LDL cholesterol and PAF-AH also were significantly higher in the lupus patients with cardiovascular disease than in those with lupus and no heart disease. Because PAF-AH binds to LDL cholesterol, it also may contribute to atherogenesis, Dr. Cederholm said.

▸ Anti-HDL-cholesterol antibodies. SLE-related dyslipidemia showed a surprising pattern in a study of women with a history of cardiovascular disease, reported J. Su, M.D. Large, rather than small, LDL- and HDL- cholesterol particles characterized the dyslipidemia profile. This was not an expected atherogenic lipid profile.

Antibodies against apolipoprotein A1 in HDL cholesterol also were elevated and were associated with the presence of tumor necrosis factor. Whether these anti-apo A1 antibodies play a pathogenic role—for example, by inhibiting the anti-inflammatory properties of HDL—is under investigation, Dr. Su said.

▸ Homocysteine. Hyperhomocysteinemia in patients with lupus correlates with markers of inflammatory activity and is a risk factor for cardiovascular disease, said Elisabet Svenungsson, M.D. In fasting blood samples obtained from a cohort of 208 patients, homocysteine levels were associated with acute phase reactants including C-reactive protein, serum amyloid A protein, fibrinogen, and complement.

Hyperhomocysteinemia also correlated with the presence of arterial disease and nephritis. “It may cause endothelial activation and damage and thus adds to the inflammatory burden that we believe renders SLE patients highly susceptible to cardiovascular disease,” she said.

BIRMINGHAM, ENGLAND — Long-term follow-up of a cohort of patients with rheumatoid arthritis who were treated with a lymphocytotoxic monoclonal antibody during the early 1990s offers reassuring support for the safety of current lymphocyte-depleting agents such as rituximab, John D. Isaacs, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

The first humanized monoclonal antibody, alemtuzumab (Campath-1H), was given to 53 patients with severe rheumatoid arthritis (RA) in the United Kingdom between 1991 and 1994.

Campath—so named because it was developed at the Cambridge University pathology laboratory—depleted both B and T cells, rendering patients profoundly lymphopenic, according to Dr. Isaacs.

This monoclonal antibody, alemtuzumab, recognizes CD52, which is present on the surface of many lymphocytes and on natural killer cells and macrophages.

“Our rationale for giving Campath to patients in the early 1990s, before [anti-tumor necrosis factor-α therapy became available, was that it would deplete the autoreactive immune system and that when reconstitution occurred the immune system would be healthy,” said Dr. Isaacs, professor of clinical rheumatology, School of Clinical Medical Sciences, University of Newcastle Upon Tyne (England).

The patients treated with Campath had severe, long-standing disease, with a median duration of 9 years. All had failed multiple disease-modifying drugs. Following one or more short courses of treatment with Campath, there was “dramatic” clinical improvement that in some cases was long lasting.

“But what we were not expecting was the lymphopenia, which ended up being quite prolonged,” he said.

During the first year after treatment, the CD4 counts were very low, and they slowly rose during the subsequent 5 years, but the levels never returned to normal. B-cell depletion was not as persistent.

In an earlier follow-up report on this group, Dr. Isaacs and his colleagues noted that 73–84 months after treatment the median CD4 count was 185 cells/μL, the median CD8 count was 95 cells/μL, and the median B-cell count was 115 cells/μL (Arthritis Rheum. 2001;44:1998–2008). This represents severe immunosuppression; the Centers for Disease Control and Prevention considers a CD4 count lower than 200 cells/μL in an HIV-positive patient a signal of AIDS.

These patients have now been followed for a mean of 12 years in a retrospective case-control study, in which outcomes for each patient were compared with two matched controls from the European League Against Rheumatism database of patients who received conventional immunosuppressive therapies such as azathioprine and cyclophosphamide.

Total follow-up is now roughly 464 patient-years.

There has been no significant difference in mortality between the two groups, with 20 deaths among the Campath cases and 37 among the controls.

Mortality also did not differ according to total dose of the monoclonal antibody or the number of courses received.

“The causes of death were primarily the complications we now associate with RA itself—vascular events and infections—and with the notable exception of one case of non-Hodgkin's lymphoma there were no infections or malignancies that one would normally associate with immunosuppression,” Dr. Isaacs said.

Despite the availability of successful therapies such as the TNF-α blockers and the fact that Campath is little used today, there still is a need for lymphocyte-depleting agents, he said.

“In fact, some of us believe that therapeutic tolerance in autoimmune disease will only become possible against a background of lymphocyte depletion,” he added.

BIRMINGHAM, ENGLAND — Long-term follow-up of a cohort of patients with rheumatoid arthritis who were treated with a lymphocytotoxic monoclonal antibody during the early 1990s offers reassuring support for the safety of current lymphocyte-depleting agents such as rituximab, John D. Isaacs, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

The first humanized monoclonal antibody, alemtuzumab (Campath-1H), was given to 53 patients with severe rheumatoid arthritis (RA) in the United Kingdom between 1991 and 1994.

Campath—so named because it was developed at the Cambridge University pathology laboratory—depleted both B and T cells, rendering patients profoundly lymphopenic, according to Dr. Isaacs.

This monoclonal antibody, alemtuzumab, recognizes CD52, which is present on the surface of many lymphocytes and on natural killer cells and macrophages.

“Our rationale for giving Campath to patients in the early 1990s, before [anti-tumor necrosis factor-α therapy became available, was that it would deplete the autoreactive immune system and that when reconstitution occurred the immune system would be healthy,” said Dr. Isaacs, professor of clinical rheumatology, School of Clinical Medical Sciences, University of Newcastle Upon Tyne (England).

The patients treated with Campath had severe, long-standing disease, with a median duration of 9 years. All had failed multiple disease-modifying drugs. Following one or more short courses of treatment with Campath, there was “dramatic” clinical improvement that in some cases was long lasting.

“But what we were not expecting was the lymphopenia, which ended up being quite prolonged,” he said.

During the first year after treatment, the CD4 counts were very low, and they slowly rose during the subsequent 5 years, but the levels never returned to normal. B-cell depletion was not as persistent.

In an earlier follow-up report on this group, Dr. Isaacs and his colleagues noted that 73–84 months after treatment the median CD4 count was 185 cells/μL, the median CD8 count was 95 cells/μL, and the median B-cell count was 115 cells/μL (Arthritis Rheum. 2001;44:1998–2008). This represents severe immunosuppression; the Centers for Disease Control and Prevention considers a CD4 count lower than 200 cells/μL in an HIV-positive patient a signal of AIDS.

These patients have now been followed for a mean of 12 years in a retrospective case-control study, in which outcomes for each patient were compared with two matched controls from the European League Against Rheumatism database of patients who received conventional immunosuppressive therapies such as azathioprine and cyclophosphamide.

Total follow-up is now roughly 464 patient-years.

There has been no significant difference in mortality between the two groups, with 20 deaths among the Campath cases and 37 among the controls.

Mortality also did not differ according to total dose of the monoclonal antibody or the number of courses received.

“The causes of death were primarily the complications we now associate with RA itself—vascular events and infections—and with the notable exception of one case of non-Hodgkin's lymphoma there were no infections or malignancies that one would normally associate with immunosuppression,” Dr. Isaacs said.

Despite the availability of successful therapies such as the TNF-α blockers and the fact that Campath is little used today, there still is a need for lymphocyte-depleting agents, he said.

“In fact, some of us believe that therapeutic tolerance in autoimmune disease will only become possible against a background of lymphocyte depletion,” he added.

BIRMINGHAM, ENGLAND — Long-term follow-up of a cohort of patients with rheumatoid arthritis who were treated with a lymphocytotoxic monoclonal antibody during the early 1990s offers reassuring support for the safety of current lymphocyte-depleting agents such as rituximab, John D. Isaacs, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

The first humanized monoclonal antibody, alemtuzumab (Campath-1H), was given to 53 patients with severe rheumatoid arthritis (RA) in the United Kingdom between 1991 and 1994.

Campath—so named because it was developed at the Cambridge University pathology laboratory—depleted both B and T cells, rendering patients profoundly lymphopenic, according to Dr. Isaacs.

This monoclonal antibody, alemtuzumab, recognizes CD52, which is present on the surface of many lymphocytes and on natural killer cells and macrophages.

“Our rationale for giving Campath to patients in the early 1990s, before [anti-tumor necrosis factor-α therapy became available, was that it would deplete the autoreactive immune system and that when reconstitution occurred the immune system would be healthy,” said Dr. Isaacs, professor of clinical rheumatology, School of Clinical Medical Sciences, University of Newcastle Upon Tyne (England).

The patients treated with Campath had severe, long-standing disease, with a median duration of 9 years. All had failed multiple disease-modifying drugs. Following one or more short courses of treatment with Campath, there was “dramatic” clinical improvement that in some cases was long lasting.

“But what we were not expecting was the lymphopenia, which ended up being quite prolonged,” he said.

During the first year after treatment, the CD4 counts were very low, and they slowly rose during the subsequent 5 years, but the levels never returned to normal. B-cell depletion was not as persistent.

In an earlier follow-up report on this group, Dr. Isaacs and his colleagues noted that 73–84 months after treatment the median CD4 count was 185 cells/μL, the median CD8 count was 95 cells/μL, and the median B-cell count was 115 cells/μL (Arthritis Rheum. 2001;44:1998–2008). This represents severe immunosuppression; the Centers for Disease Control and Prevention considers a CD4 count lower than 200 cells/μL in an HIV-positive patient a signal of AIDS.

These patients have now been followed for a mean of 12 years in a retrospective case-control study, in which outcomes for each patient were compared with two matched controls from the European League Against Rheumatism database of patients who received conventional immunosuppressive therapies such as azathioprine and cyclophosphamide.

Total follow-up is now roughly 464 patient-years.

There has been no significant difference in mortality between the two groups, with 20 deaths among the Campath cases and 37 among the controls.

Mortality also did not differ according to total dose of the monoclonal antibody or the number of courses received.

“The causes of death were primarily the complications we now associate with RA itself—vascular events and infections—and with the notable exception of one case of non-Hodgkin's lymphoma there were no infections or malignancies that one would normally associate with immunosuppression,” Dr. Isaacs said.

Despite the availability of successful therapies such as the TNF-α blockers and the fact that Campath is little used today, there still is a need for lymphocyte-depleting agents, he said.

“In fact, some of us believe that therapeutic tolerance in autoimmune disease will only become possible against a background of lymphocyte depletion,” he added.