Psoriasis Collection

PsoriasisDX, the first commercially available genetic test for psoriatic arthritis, can help detect the condition before symptoms develop, allowing for less joint damage through early treatment. This is important because medications for psoriatic arthritis can prevent joint destruction but not reverse damage once it occurs. Using the PsoriasisDX Genetic Test kit, a cheek swab sample is sent to the laboratory for analysis. The gene variant MICA-A9 is found in approximately 60% of those who develop PsA; if the variant is not present, the patient has an approximately 70% chance of not getting the condition. The kit is $399 and available through qualified physicians.

PsoriasisDX

www.psoriasisdx.com

PsoriasisDX, the first commercially available genetic test for psoriatic arthritis, can help detect the condition before symptoms develop, allowing for less joint damage through early treatment. This is important because medications for psoriatic arthritis can prevent joint destruction but not reverse damage once it occurs. Using the PsoriasisDX Genetic Test kit, a cheek swab sample is sent to the laboratory for analysis. The gene variant MICA-A9 is found in approximately 60% of those who develop PsA; if the variant is not present, the patient has an approximately 70% chance of not getting the condition. The kit is $399 and available through qualified physicians.

PsoriasisDX

www.psoriasisdx.com

PsoriasisDX, the first commercially available genetic test for psoriatic arthritis, can help detect the condition before symptoms develop, allowing for less joint damage through early treatment. This is important because medications for psoriatic arthritis can prevent joint destruction but not reverse damage once it occurs. Using the PsoriasisDX Genetic Test kit, a cheek swab sample is sent to the laboratory for analysis. The gene variant MICA-A9 is found in approximately 60% of those who develop PsA; if the variant is not present, the patient has an approximately 70% chance of not getting the condition. The kit is $399 and available through qualified physicians.

PsoriasisDX

www.psoriasisdx.com

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

The OTIS study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500, said Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease.

Many participants are referred to the OTIS coordinating center, where they undergo multiple interviews and review of their symptom management. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians, undergo blinded dysmorphological examination by OTIS physicians, and are photographed.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. While the literature contains case reports, the OTIS Project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared with 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percent of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%) and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%).

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. The defects included displaced stomach with epispadias and congenital eye defect; ventricular septal defect with peripheral pulmonic stenosis; pyloric stenosis; hypospadias; ventricular septal defect with patent foramen ovale and patent ductus arteriosus; volvulus; patent foramen ovale; atrial septal defect with patent ductus arteriosus; microcephaly; congenital hypothyroidism; and an unspecified heart defect. Three abnormalities—Noonan syndrome, Turner syndrome, and Down syndrome—were genetic or chromosomal. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%). There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups compared with healthy controls (4%). Mean birth weight was approximately 300 grams less in full term infants whose mothers had received adalimumab compared with healthy controls but similar to full-term infants in the disease-matched comparison group.

Rates of major malformations were similar (from 4% to 5%) in all groups and within the range of expected numbers in the general population, said Dr. Chambers.

My Take

Answering Your Patient's Questions

There are really sparse data on the safety of biologic agents in women who are pregnant. We currently are in a situation where controlled randomized trials typically are not appropriate, yet pregnant women are using these medications. The OTIS project is a prospective, observational cohort study that should shed light on whether biologics are safe for women who are pregnant. However, it will still be several years before all results are in and the data can be statistically analyzed. In the meantime, what can you tell your patients about the use of biologics if they are pregnant or plan to become pregnant?

Q: If I take a biologic, will it be more difficult to become pregnant?

A: Information is very limited, but to date neither preclinical data nor clinical data indicate that becoming pregnant is more difficult.

Q. If I do become pregnant while on a biologic drug, do I have a chance of having a baby with a birth defect?

A. One of the principles of teratology is that known teratogens tend to cause specific patterns of malformations. To date with the limited information available, neither animal nor human data suggest that the risk for a specific pattern of defects is increased over baseline if you take a biologic agent while pregnant. While preliminary results from the OTIS project have noted that more malformations occurred in the offspring of women taking etanercept, the defects were varied and isolated.

Q. If I do become pregnant while taking this drug, will my child's immune system be compromised?

A. There are limited human data available for rituximab. To date, the results of the OTIS study do not indicate an increase in opportunistic infections, hospitalizations, or malignancies in the infants of women who have taken etanercept or adalimumab.

Q. If I do become pregnant while taking a biologic agent, do I have to discontinue the drug or can I safely continue to take the drug throughout pregnancy?

A. We really don't know the answer. In the OTIS project, approximately half of women on etanercept or adalimumab remain on the medication into the second or third trimester.

Disclosures: Dr. Chambers has received research grants from Sandoz, Kali Labs, Apotex, Barr Labs, Teva Pharmaceuticals, Amgen, Bristol Myers Squibb, Abbott Laboratories, Sanofi-Aventis Pharmaceutical, and Sanofi-Pasteur.

BY CHRISTINA CHAMBERS, Ph.D.

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

The OTIS study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500, said Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease.

Many participants are referred to the OTIS coordinating center, where they undergo multiple interviews and review of their symptom management. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians, undergo blinded dysmorphological examination by OTIS physicians, and are photographed.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. While the literature contains case reports, the OTIS Project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared with 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percent of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%) and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%).

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. The defects included displaced stomach with epispadias and congenital eye defect; ventricular septal defect with peripheral pulmonic stenosis; pyloric stenosis; hypospadias; ventricular septal defect with patent foramen ovale and patent ductus arteriosus; volvulus; patent foramen ovale; atrial septal defect with patent ductus arteriosus; microcephaly; congenital hypothyroidism; and an unspecified heart defect. Three abnormalities—Noonan syndrome, Turner syndrome, and Down syndrome—were genetic or chromosomal. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%). There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups compared with healthy controls (4%). Mean birth weight was approximately 300 grams less in full term infants whose mothers had received adalimumab compared with healthy controls but similar to full-term infants in the disease-matched comparison group.

Rates of major malformations were similar (from 4% to 5%) in all groups and within the range of expected numbers in the general population, said Dr. Chambers.

My Take

Answering Your Patient's Questions

There are really sparse data on the safety of biologic agents in women who are pregnant. We currently are in a situation where controlled randomized trials typically are not appropriate, yet pregnant women are using these medications. The OTIS project is a prospective, observational cohort study that should shed light on whether biologics are safe for women who are pregnant. However, it will still be several years before all results are in and the data can be statistically analyzed. In the meantime, what can you tell your patients about the use of biologics if they are pregnant or plan to become pregnant?

Q: If I take a biologic, will it be more difficult to become pregnant?

A: Information is very limited, but to date neither preclinical data nor clinical data indicate that becoming pregnant is more difficult.

Q. If I do become pregnant while on a biologic drug, do I have a chance of having a baby with a birth defect?

A. One of the principles of teratology is that known teratogens tend to cause specific patterns of malformations. To date with the limited information available, neither animal nor human data suggest that the risk for a specific pattern of defects is increased over baseline if you take a biologic agent while pregnant. While preliminary results from the OTIS project have noted that more malformations occurred in the offspring of women taking etanercept, the defects were varied and isolated.

Q. If I do become pregnant while taking this drug, will my child's immune system be compromised?

A. There are limited human data available for rituximab. To date, the results of the OTIS study do not indicate an increase in opportunistic infections, hospitalizations, or malignancies in the infants of women who have taken etanercept or adalimumab.

Q. If I do become pregnant while taking a biologic agent, do I have to discontinue the drug or can I safely continue to take the drug throughout pregnancy?

A. We really don't know the answer. In the OTIS project, approximately half of women on etanercept or adalimumab remain on the medication into the second or third trimester.

Disclosures: Dr. Chambers has received research grants from Sandoz, Kali Labs, Apotex, Barr Labs, Teva Pharmaceuticals, Amgen, Bristol Myers Squibb, Abbott Laboratories, Sanofi-Aventis Pharmaceutical, and Sanofi-Pasteur.

BY CHRISTINA CHAMBERS, Ph.D.

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

The OTIS study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500, said Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease.

Many participants are referred to the OTIS coordinating center, where they undergo multiple interviews and review of their symptom management. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians, undergo blinded dysmorphological examination by OTIS physicians, and are photographed.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. While the literature contains case reports, the OTIS Project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared with 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percent of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%) and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%).

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. The defects included displaced stomach with epispadias and congenital eye defect; ventricular septal defect with peripheral pulmonic stenosis; pyloric stenosis; hypospadias; ventricular septal defect with patent foramen ovale and patent ductus arteriosus; volvulus; patent foramen ovale; atrial septal defect with patent ductus arteriosus; microcephaly; congenital hypothyroidism; and an unspecified heart defect. Three abnormalities—Noonan syndrome, Turner syndrome, and Down syndrome—were genetic or chromosomal. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%). There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups compared with healthy controls (4%). Mean birth weight was approximately 300 grams less in full term infants whose mothers had received adalimumab compared with healthy controls but similar to full-term infants in the disease-matched comparison group.

Rates of major malformations were similar (from 4% to 5%) in all groups and within the range of expected numbers in the general population, said Dr. Chambers.

My Take

Answering Your Patient's Questions

There are really sparse data on the safety of biologic agents in women who are pregnant. We currently are in a situation where controlled randomized trials typically are not appropriate, yet pregnant women are using these medications. The OTIS project is a prospective, observational cohort study that should shed light on whether biologics are safe for women who are pregnant. However, it will still be several years before all results are in and the data can be statistically analyzed. In the meantime, what can you tell your patients about the use of biologics if they are pregnant or plan to become pregnant?

Q: If I take a biologic, will it be more difficult to become pregnant?

A: Information is very limited, but to date neither preclinical data nor clinical data indicate that becoming pregnant is more difficult.

Q. If I do become pregnant while on a biologic drug, do I have a chance of having a baby with a birth defect?

A. One of the principles of teratology is that known teratogens tend to cause specific patterns of malformations. To date with the limited information available, neither animal nor human data suggest that the risk for a specific pattern of defects is increased over baseline if you take a biologic agent while pregnant. While preliminary results from the OTIS project have noted that more malformations occurred in the offspring of women taking etanercept, the defects were varied and isolated.

Q. If I do become pregnant while taking this drug, will my child's immune system be compromised?

A. There are limited human data available for rituximab. To date, the results of the OTIS study do not indicate an increase in opportunistic infections, hospitalizations, or malignancies in the infants of women who have taken etanercept or adalimumab.

Q. If I do become pregnant while taking a biologic agent, do I have to discontinue the drug or can I safely continue to take the drug throughout pregnancy?

A. We really don't know the answer. In the OTIS project, approximately half of women on etanercept or adalimumab remain on the medication into the second or third trimester.

Disclosures: Dr. Chambers has received research grants from Sandoz, Kali Labs, Apotex, Barr Labs, Teva Pharmaceuticals, Amgen, Bristol Myers Squibb, Abbott Laboratories, Sanofi-Aventis Pharmaceutical, and Sanofi-Pasteur.

BY CHRISTINA CHAMBERS, Ph.D.

PHILADELPHIA — Treatment with golimumab reversed structural joint damage in patients with psoriatic arthritis in a placebo-controlled, phase III study of over 400 patients.

The structural joint benefit from golimumab in this analysis complemented clinical improvements previously reported from the same study. Those benefits led the Food and Drug Administration to give marketing approval to golimumab for psoriatic arthritis (PsA) last April.

The results showed structural improvement with golimumab after 24 weeks of treatment, the primary end point of the radiographic assessment, independent of methotrexate cotreatment. The benefit continued through 52 weeks of follow-up, Dr. Arthur F. Kavanaugh said at the annual meeting of the American College of Rheumatology (ACR).

The GO-REVEAL (Golimumab—A Randomized Evaluation of Safety and Efficacy in Subjects With Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody) study enrolled patients at 58 sites in the United States, Canada, and Europe, and was the largest completed study of its kind (405 patients) with a biologic agent in patients with PsA. Enrolled patients had active disease despite treatment with disease-modifying drugs or nonsteroidal anti-inflammatory drugs. Their average age was 47 years, their average duration of PsA was 8 years, 60% were men, 97% were white, and 48% were on methotrexate treatment.

Patients received injections of 50 mg golimumab (146 patients), 100 mg golimumab (146 patients), or placebo (113 patients) at week 0, and then every 4 weeks through week 20. Starting at week 24, all patients received golimumab.

The clinical outcomes published last April showed that treatment with golimumab led to an ACR 20 response in 51% of patients on the 50-mg dose and in 45% of those receiving a 100-mg dose at week 14, compared with 9% of placebo patients (Arthritis Rheum. 2009;60:976-86).

The new analysis used total Sharp/van der Heijde score to measure structural joint damage. At baseline, average scores were 18 in placebo patients, 24 in the 50-mg group, and 23 in the 100-mg group.

After 24 weeks, the scores changed by an average of +0.27 in the placebo patients (a worsening), −0.16 in patients getting 50-mg doses, and −0.02 in those on 100-mg doses. The difference between the 50-mg group and placebo patients was statistically significant. The difference between the 100-mg and placebo group did not reach statistical significance, said Dr. Kavanaugh, a professor of clinical medicine at the University of California, San Diego. The difference in average Sharp/van der Heijde scores between the placebo patients and those in both golimumab groups continued through 52 weeks of treatment, even though the placebo patients switched to golimumab treatment after the first 24 weeks of the study.

The golimumab GO-REVEAL study was the largest completed study of its kind with a biologic agent in patients with PsA.

Source DR. KAVANAUGH

Vitals

Major Finding: Structural improvement continued through 52 weeks with golimumab, independent of methotrexate.

Source of Data: The GO-REVEAL study enrolled 405 patients at 58 sites in the United States, Canada, and Europe.

Disclosures: Centocor Ortho Biotech Products LP, the company that developed and now markets golimumab (Simponi), sponsored the study. Dr. Kavanaugh said that he and five of his associates on the study were researcher investigators for Centocor. Another five study associates are Centocor employees.

PHILADELPHIA — Treatment with golimumab reversed structural joint damage in patients with psoriatic arthritis in a placebo-controlled, phase III study of over 400 patients.

The structural joint benefit from golimumab in this analysis complemented clinical improvements previously reported from the same study. Those benefits led the Food and Drug Administration to give marketing approval to golimumab for psoriatic arthritis (PsA) last April.

The results showed structural improvement with golimumab after 24 weeks of treatment, the primary end point of the radiographic assessment, independent of methotrexate cotreatment. The benefit continued through 52 weeks of follow-up, Dr. Arthur F. Kavanaugh said at the annual meeting of the American College of Rheumatology (ACR).

The GO-REVEAL (Golimumab—A Randomized Evaluation of Safety and Efficacy in Subjects With Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody) study enrolled patients at 58 sites in the United States, Canada, and Europe, and was the largest completed study of its kind (405 patients) with a biologic agent in patients with PsA. Enrolled patients had active disease despite treatment with disease-modifying drugs or nonsteroidal anti-inflammatory drugs. Their average age was 47 years, their average duration of PsA was 8 years, 60% were men, 97% were white, and 48% were on methotrexate treatment.

Patients received injections of 50 mg golimumab (146 patients), 100 mg golimumab (146 patients), or placebo (113 patients) at week 0, and then every 4 weeks through week 20. Starting at week 24, all patients received golimumab.

The clinical outcomes published last April showed that treatment with golimumab led to an ACR 20 response in 51% of patients on the 50-mg dose and in 45% of those receiving a 100-mg dose at week 14, compared with 9% of placebo patients (Arthritis Rheum. 2009;60:976-86).

The new analysis used total Sharp/van der Heijde score to measure structural joint damage. At baseline, average scores were 18 in placebo patients, 24 in the 50-mg group, and 23 in the 100-mg group.

After 24 weeks, the scores changed by an average of +0.27 in the placebo patients (a worsening), −0.16 in patients getting 50-mg doses, and −0.02 in those on 100-mg doses. The difference between the 50-mg group and placebo patients was statistically significant. The difference between the 100-mg and placebo group did not reach statistical significance, said Dr. Kavanaugh, a professor of clinical medicine at the University of California, San Diego. The difference in average Sharp/van der Heijde scores between the placebo patients and those in both golimumab groups continued through 52 weeks of treatment, even though the placebo patients switched to golimumab treatment after the first 24 weeks of the study.

The golimumab GO-REVEAL study was the largest completed study of its kind with a biologic agent in patients with PsA.

Source DR. KAVANAUGH

Vitals

Major Finding: Structural improvement continued through 52 weeks with golimumab, independent of methotrexate.

Source of Data: The GO-REVEAL study enrolled 405 patients at 58 sites in the United States, Canada, and Europe.

Disclosures: Centocor Ortho Biotech Products LP, the company that developed and now markets golimumab (Simponi), sponsored the study. Dr. Kavanaugh said that he and five of his associates on the study were researcher investigators for Centocor. Another five study associates are Centocor employees.

PHILADELPHIA — Treatment with golimumab reversed structural joint damage in patients with psoriatic arthritis in a placebo-controlled, phase III study of over 400 patients.

The structural joint benefit from golimumab in this analysis complemented clinical improvements previously reported from the same study. Those benefits led the Food and Drug Administration to give marketing approval to golimumab for psoriatic arthritis (PsA) last April.

The results showed structural improvement with golimumab after 24 weeks of treatment, the primary end point of the radiographic assessment, independent of methotrexate cotreatment. The benefit continued through 52 weeks of follow-up, Dr. Arthur F. Kavanaugh said at the annual meeting of the American College of Rheumatology (ACR).

The GO-REVEAL (Golimumab—A Randomized Evaluation of Safety and Efficacy in Subjects With Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody) study enrolled patients at 58 sites in the United States, Canada, and Europe, and was the largest completed study of its kind (405 patients) with a biologic agent in patients with PsA. Enrolled patients had active disease despite treatment with disease-modifying drugs or nonsteroidal anti-inflammatory drugs. Their average age was 47 years, their average duration of PsA was 8 years, 60% were men, 97% were white, and 48% were on methotrexate treatment.

Patients received injections of 50 mg golimumab (146 patients), 100 mg golimumab (146 patients), or placebo (113 patients) at week 0, and then every 4 weeks through week 20. Starting at week 24, all patients received golimumab.

The clinical outcomes published last April showed that treatment with golimumab led to an ACR 20 response in 51% of patients on the 50-mg dose and in 45% of those receiving a 100-mg dose at week 14, compared with 9% of placebo patients (Arthritis Rheum. 2009;60:976-86).

The new analysis used total Sharp/van der Heijde score to measure structural joint damage. At baseline, average scores were 18 in placebo patients, 24 in the 50-mg group, and 23 in the 100-mg group.

After 24 weeks, the scores changed by an average of +0.27 in the placebo patients (a worsening), −0.16 in patients getting 50-mg doses, and −0.02 in those on 100-mg doses. The difference between the 50-mg group and placebo patients was statistically significant. The difference between the 100-mg and placebo group did not reach statistical significance, said Dr. Kavanaugh, a professor of clinical medicine at the University of California, San Diego. The difference in average Sharp/van der Heijde scores between the placebo patients and those in both golimumab groups continued through 52 weeks of treatment, even though the placebo patients switched to golimumab treatment after the first 24 weeks of the study.

The golimumab GO-REVEAL study was the largest completed study of its kind with a biologic agent in patients with PsA.

Source DR. KAVANAUGH

Vitals

Major Finding: Structural improvement continued through 52 weeks with golimumab, independent of methotrexate.

Source of Data: The GO-REVEAL study enrolled 405 patients at 58 sites in the United States, Canada, and Europe.

Disclosures: Centocor Ortho Biotech Products LP, the company that developed and now markets golimumab (Simponi), sponsored the study. Dr. Kavanaugh said that he and five of his associates on the study were researcher investigators for Centocor. Another five study associates are Centocor employees.

BERLIN — Bosentan appears to be effective for reduction of skin fibrosis in patients with systemic sclerosis.

Ten patients with systemic sclerosis showed a significant decrease in the skin-thickening characteristic of the disease in response to treatment with bosentan (Tracleer) in a prospective open-label study, Dr. Annegret Kuhn reported at the annual congress of the European Academy of Dermatology and Venereology.

All 10 patients showed significant improvement, with a mean 6.4-point reduction in the Rodnan Skin Score at 24 weeks, which was the primary study end point, according to Dr. Kuhn of the University of Müenster (Germany).

Patients with diffuse systemic sclerosis had a mean 7.8-point reduction, while those with limited systemic sclerosis averaged a 6.3-point improvement in Rodnan Skin Score.

Participants in this small uncontrolled trial also experienced significant healing of digital ulcers, with reduction in size and, in some cases, outright healing. In contrast, Dr. Kuhn noted, the 122-patient double-blind Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Scleroderma (RAPIDS-1) showed that the number of new digital ulcers was reduced by half with bosentan, compared with placebo, but that healing of existing ulcers wasn't expedited (Arthritis Rheum. 2004;50:3985-93).

In the current study, favorable trends on the Scleroderma Health Assessment Questionnaire and the UK SSc Functional Score were documented over the course of 24 weeks but didn't achieve statistical significance. There were no consistent changes over time in terms of 20-MHz ultrasound or hand functioning as assessed by the fist closure test.

Bosentan was dosed at 62.5 mg twice daily for the first 4 weeks, then 125 mg twice daily. The dual endothelin receptor antagonist is approved for treatment of pulmonary arterial hypertension. The European Medicines Agency has granted bosentan orphan drug status for the treatment of patients with systemic sclerosis.

Disclosures: Dr. Kuhn's study was funded by Actelion, the manufacturer of bosentan.

BERLIN — Bosentan appears to be effective for reduction of skin fibrosis in patients with systemic sclerosis.

Ten patients with systemic sclerosis showed a significant decrease in the skin-thickening characteristic of the disease in response to treatment with bosentan (Tracleer) in a prospective open-label study, Dr. Annegret Kuhn reported at the annual congress of the European Academy of Dermatology and Venereology.

All 10 patients showed significant improvement, with a mean 6.4-point reduction in the Rodnan Skin Score at 24 weeks, which was the primary study end point, according to Dr. Kuhn of the University of Müenster (Germany).

Patients with diffuse systemic sclerosis had a mean 7.8-point reduction, while those with limited systemic sclerosis averaged a 6.3-point improvement in Rodnan Skin Score.

Participants in this small uncontrolled trial also experienced significant healing of digital ulcers, with reduction in size and, in some cases, outright healing. In contrast, Dr. Kuhn noted, the 122-patient double-blind Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Scleroderma (RAPIDS-1) showed that the number of new digital ulcers was reduced by half with bosentan, compared with placebo, but that healing of existing ulcers wasn't expedited (Arthritis Rheum. 2004;50:3985-93).

In the current study, favorable trends on the Scleroderma Health Assessment Questionnaire and the UK SSc Functional Score were documented over the course of 24 weeks but didn't achieve statistical significance. There were no consistent changes over time in terms of 20-MHz ultrasound or hand functioning as assessed by the fist closure test.

Bosentan was dosed at 62.5 mg twice daily for the first 4 weeks, then 125 mg twice daily. The dual endothelin receptor antagonist is approved for treatment of pulmonary arterial hypertension. The European Medicines Agency has granted bosentan orphan drug status for the treatment of patients with systemic sclerosis.

Disclosures: Dr. Kuhn's study was funded by Actelion, the manufacturer of bosentan.

BERLIN — Bosentan appears to be effective for reduction of skin fibrosis in patients with systemic sclerosis.

Ten patients with systemic sclerosis showed a significant decrease in the skin-thickening characteristic of the disease in response to treatment with bosentan (Tracleer) in a prospective open-label study, Dr. Annegret Kuhn reported at the annual congress of the European Academy of Dermatology and Venereology.

All 10 patients showed significant improvement, with a mean 6.4-point reduction in the Rodnan Skin Score at 24 weeks, which was the primary study end point, according to Dr. Kuhn of the University of Müenster (Germany).

Patients with diffuse systemic sclerosis had a mean 7.8-point reduction, while those with limited systemic sclerosis averaged a 6.3-point improvement in Rodnan Skin Score.

Participants in this small uncontrolled trial also experienced significant healing of digital ulcers, with reduction in size and, in some cases, outright healing. In contrast, Dr. Kuhn noted, the 122-patient double-blind Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Scleroderma (RAPIDS-1) showed that the number of new digital ulcers was reduced by half with bosentan, compared with placebo, but that healing of existing ulcers wasn't expedited (Arthritis Rheum. 2004;50:3985-93).

In the current study, favorable trends on the Scleroderma Health Assessment Questionnaire and the UK SSc Functional Score were documented over the course of 24 weeks but didn't achieve statistical significance. There were no consistent changes over time in terms of 20-MHz ultrasound or hand functioning as assessed by the fist closure test.

Bosentan was dosed at 62.5 mg twice daily for the first 4 weeks, then 125 mg twice daily. The dual endothelin receptor antagonist is approved for treatment of pulmonary arterial hypertension. The European Medicines Agency has granted bosentan orphan drug status for the treatment of patients with systemic sclerosis.

Disclosures: Dr. Kuhn's study was funded by Actelion, the manufacturer of bosentan.

BERLIN — Clonal T cell populations may play a key role in the pathogenesis of systemic sclerosis.

Expanded populations of clonal T cells were detected by high-resolution capillary electrophoresis and polymerase chain reaction in the peripheral blood of 61% of 126 patients with systemic sclerosis, Dr. Alexander Kreuter reported at the annual congress of the European Academy of Dermatology and Venereology.

Expanded clonal T cells were particularly common in the setting of limited cutaneous systemic sclerosis: They were detected using high-resolution capillary electrophoresis and polymerase chain reaction testing in 48 of 65 (74%) of affected patients, in contrast to 29 of 61 patients (48%) with diffuse cutaneous systemic sclerosis, said Dr. Kreuter, a dermatologist at Ruhr University in Bochum, Germany.

The likelihood that these circulating clonal T-cell populations are involved in the pathogenesis of systemic sclerosis is enhanced by the finding that a clonal T-cell population was detected in the peripheral circulation of only 4 of 29 (14%) of healthy controls, he added. Twenty of 44 systemic sclerosis patients (46%) had clonal T-cell populations in lesional skin specimens. The presence of lesional clonal T cells was unrelated to the presence or absence of circulating clonal T cells.

The presence of clonal T-cell populations in the peripheral circulation was unrelated to sex, disease duration, extent of skin involvement, digital ulcers, organ involvement, autoantibody profile, or the form of treatment employed.

Disclosures: Dr. Kreuter reported no financial conflicts.

BERLIN — Clonal T cell populations may play a key role in the pathogenesis of systemic sclerosis.

Expanded populations of clonal T cells were detected by high-resolution capillary electrophoresis and polymerase chain reaction in the peripheral blood of 61% of 126 patients with systemic sclerosis, Dr. Alexander Kreuter reported at the annual congress of the European Academy of Dermatology and Venereology.

Expanded clonal T cells were particularly common in the setting of limited cutaneous systemic sclerosis: They were detected using high-resolution capillary electrophoresis and polymerase chain reaction testing in 48 of 65 (74%) of affected patients, in contrast to 29 of 61 patients (48%) with diffuse cutaneous systemic sclerosis, said Dr. Kreuter, a dermatologist at Ruhr University in Bochum, Germany.

The likelihood that these circulating clonal T-cell populations are involved in the pathogenesis of systemic sclerosis is enhanced by the finding that a clonal T-cell population was detected in the peripheral circulation of only 4 of 29 (14%) of healthy controls, he added. Twenty of 44 systemic sclerosis patients (46%) had clonal T-cell populations in lesional skin specimens. The presence of lesional clonal T cells was unrelated to the presence or absence of circulating clonal T cells.

The presence of clonal T-cell populations in the peripheral circulation was unrelated to sex, disease duration, extent of skin involvement, digital ulcers, organ involvement, autoantibody profile, or the form of treatment employed.

Disclosures: Dr. Kreuter reported no financial conflicts.

BERLIN — Clonal T cell populations may play a key role in the pathogenesis of systemic sclerosis.

Expanded populations of clonal T cells were detected by high-resolution capillary electrophoresis and polymerase chain reaction in the peripheral blood of 61% of 126 patients with systemic sclerosis, Dr. Alexander Kreuter reported at the annual congress of the European Academy of Dermatology and Venereology.

Expanded clonal T cells were particularly common in the setting of limited cutaneous systemic sclerosis: They were detected using high-resolution capillary electrophoresis and polymerase chain reaction testing in 48 of 65 (74%) of affected patients, in contrast to 29 of 61 patients (48%) with diffuse cutaneous systemic sclerosis, said Dr. Kreuter, a dermatologist at Ruhr University in Bochum, Germany.

The likelihood that these circulating clonal T-cell populations are involved in the pathogenesis of systemic sclerosis is enhanced by the finding that a clonal T-cell population was detected in the peripheral circulation of only 4 of 29 (14%) of healthy controls, he added. Twenty of 44 systemic sclerosis patients (46%) had clonal T-cell populations in lesional skin specimens. The presence of lesional clonal T cells was unrelated to the presence or absence of circulating clonal T cells.

The presence of clonal T-cell populations in the peripheral circulation was unrelated to sex, disease duration, extent of skin involvement, digital ulcers, organ involvement, autoantibody profile, or the form of treatment employed.

Disclosures: Dr. Kreuter reported no financial conflicts.

New guidelines issued by the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and recommendations for the design of observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix to the document contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, according to Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included dermatologists, rheumatologists, internists, and a nephrologist. They arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity, using a validated index; quality of life, determined either by history alone or in addition to a patient-completed measure such as a 0-10 visual analog scale; and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease (CVD), including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients also need yearly blood tests for blood cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking habit. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including Pap smears) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus, especially before the start of immunosuppressive drugs; for tuberculosis, according to local guidelines and especially before the initiation of immunosuppressive drugs; and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the Centers for Disease Control and Prevention. It is ideal to do the immunization when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. For the exact risk of infection to be determined, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of clinical and laboratory assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)–specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if there is a change in the clinical morphology of the lesions, or if there is a lack of response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org).

▸ Neuropsychiatric manifestations. Neurologic involvement (central, peripheral, or autonomic) occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult and no specific instrument has been evaluated in clinical practice. Therefore, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82).

Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

In most cases, anything left out of these recommendations should be considered part of standard good clinical practice. In some cases, items were not addressed because of contradictory evidence, wrote the authors, who also included an agenda for future research.

New guidelines issued by the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and recommendations for the design of observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix to the document contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, according to Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included dermatologists, rheumatologists, internists, and a nephrologist. They arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity, using a validated index; quality of life, determined either by history alone or in addition to a patient-completed measure such as a 0-10 visual analog scale; and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease (CVD), including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients also need yearly blood tests for blood cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking habit. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including Pap smears) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus, especially before the start of immunosuppressive drugs; for tuberculosis, according to local guidelines and especially before the initiation of immunosuppressive drugs; and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the Centers for Disease Control and Prevention. It is ideal to do the immunization when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. For the exact risk of infection to be determined, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of clinical and laboratory assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)–specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if there is a change in the clinical morphology of the lesions, or if there is a lack of response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org).

▸ Neuropsychiatric manifestations. Neurologic involvement (central, peripheral, or autonomic) occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult and no specific instrument has been evaluated in clinical practice. Therefore, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82).

Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

In most cases, anything left out of these recommendations should be considered part of standard good clinical practice. In some cases, items were not addressed because of contradictory evidence, wrote the authors, who also included an agenda for future research.

New guidelines issued by the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and recommendations for the design of observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix to the document contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, according to Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included dermatologists, rheumatologists, internists, and a nephrologist. They arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity, using a validated index; quality of life, determined either by history alone or in addition to a patient-completed measure such as a 0-10 visual analog scale; and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease (CVD), including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients also need yearly blood tests for blood cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking habit. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including Pap smears) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus, especially before the start of immunosuppressive drugs; for tuberculosis, according to local guidelines and especially before the initiation of immunosuppressive drugs; and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the Centers for Disease Control and Prevention. It is ideal to do the immunization when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. For the exact risk of infection to be determined, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of clinical and laboratory assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)–specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if there is a change in the clinical morphology of the lesions, or if there is a lack of response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org).

▸ Neuropsychiatric manifestations. Neurologic involvement (central, peripheral, or autonomic) occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult and no specific instrument has been evaluated in clinical practice. Therefore, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82).

Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

In most cases, anything left out of these recommendations should be considered part of standard good clinical practice. In some cases, items were not addressed because of contradictory evidence, wrote the authors, who also included an agenda for future research.

PHILADELPHIA — Two studies showed an increased risk for nonmelanoma skin cancer in patients who take anti–tumor necrosis factor therapies, and should prompt physicians to evaluate the use of these drugs in patients who are at risk for skin cancer, according to the researchers.

Previous studies have been too small to show a definitive link between biologic therapy for rheumatoid arthritis (RA) and skin malignancy, although RA previously has been well established as a risk factor for skin cancer, according to Dr. Prahba Ranganathan.

She presented the results of her retrospective cohort study of RA patients in the Department of Veterans Affairs national database at the annual meeting of the American College of Rheumatology.

According to Dr. Ranganathan, among 16,829 patients with RA, 3,096 were treated with anti-TNFs at the VA between Oct. 1, 1998, and Sept. 30, 2006. The incidence of nonmelanoma skin cancer was 25.9 per 1,000 patient-years in this cohort, compared with 19.6 per 1,000 patient-years in the biologic-naive cohort, a 34% increased risk.

The incidence of melanoma also was increased by about 50%, with about 3.7 cases per 1,000 patient-years seen in the anti-TNF-treated group, vs. 2.6 cases per 1,000 patient-years in the biologic-naive cohort. Both results were significant.

A second study presented at the press conference confirmed these findings. Dr. Kimme Hyrich of the University of Manchester (England) looked at RA patients from the British Society for Rheumatology's biologics register, a prospective cohort study begun in 2001 to monitor the long-term safety of anti-TNFs.

Dr. Hyrich found that among 11,598 RA patients who were treated with anti-TNFs and had no prior nonmelanoma skin cancer, the incidence of a malignancy was 3.5 per 1,000 patient-years. In contrast, among 8,975 similar patients who were treated with nonbiologic therapies, the incidence of new nonmelanoma skin cancers was 2.4.

That was a 70% increased risk for the anti-TNF–treated patients, although the data were not significant, Dr. Hyrich reported.

Dr. Hyrich pointed out that patients treated with anti-TNF drugs typically have more contact with their physicians, which could have introduced a surveillance bias.

Dr. Ranganathan cautioned that even in patients with multiple skin cancer risks anti-TNFs are still a good choice for patients who've failed other treatments. “People with risk factors should be watched more closely and maybe have periodic skin exams,” she said.

Dr. Ranganathan, Dr. Hyrich, and their respective research teams did not report having any financial conflicts relative to their studies.

PHILADELPHIA — Two studies showed an increased risk for nonmelanoma skin cancer in patients who take anti–tumor necrosis factor therapies, and should prompt physicians to evaluate the use of these drugs in patients who are at risk for skin cancer, according to the researchers.

Previous studies have been too small to show a definitive link between biologic therapy for rheumatoid arthritis (RA) and skin malignancy, although RA previously has been well established as a risk factor for skin cancer, according to Dr. Prahba Ranganathan.

She presented the results of her retrospective cohort study of RA patients in the Department of Veterans Affairs national database at the annual meeting of the American College of Rheumatology.

According to Dr. Ranganathan, among 16,829 patients with RA, 3,096 were treated with anti-TNFs at the VA between Oct. 1, 1998, and Sept. 30, 2006. The incidence of nonmelanoma skin cancer was 25.9 per 1,000 patient-years in this cohort, compared with 19.6 per 1,000 patient-years in the biologic-naive cohort, a 34% increased risk.

The incidence of melanoma also was increased by about 50%, with about 3.7 cases per 1,000 patient-years seen in the anti-TNF-treated group, vs. 2.6 cases per 1,000 patient-years in the biologic-naive cohort. Both results were significant.

A second study presented at the press conference confirmed these findings. Dr. Kimme Hyrich of the University of Manchester (England) looked at RA patients from the British Society for Rheumatology's biologics register, a prospective cohort study begun in 2001 to monitor the long-term safety of anti-TNFs.

Dr. Hyrich found that among 11,598 RA patients who were treated with anti-TNFs and had no prior nonmelanoma skin cancer, the incidence of a malignancy was 3.5 per 1,000 patient-years. In contrast, among 8,975 similar patients who were treated with nonbiologic therapies, the incidence of new nonmelanoma skin cancers was 2.4.

That was a 70% increased risk for the anti-TNF–treated patients, although the data were not significant, Dr. Hyrich reported.

Dr. Hyrich pointed out that patients treated with anti-TNF drugs typically have more contact with their physicians, which could have introduced a surveillance bias.

Dr. Ranganathan cautioned that even in patients with multiple skin cancer risks anti-TNFs are still a good choice for patients who've failed other treatments. “People with risk factors should be watched more closely and maybe have periodic skin exams,” she said.

Dr. Ranganathan, Dr. Hyrich, and their respective research teams did not report having any financial conflicts relative to their studies.

PHILADELPHIA — Two studies showed an increased risk for nonmelanoma skin cancer in patients who take anti–tumor necrosis factor therapies, and should prompt physicians to evaluate the use of these drugs in patients who are at risk for skin cancer, according to the researchers.

Previous studies have been too small to show a definitive link between biologic therapy for rheumatoid arthritis (RA) and skin malignancy, although RA previously has been well established as a risk factor for skin cancer, according to Dr. Prahba Ranganathan.

She presented the results of her retrospective cohort study of RA patients in the Department of Veterans Affairs national database at the annual meeting of the American College of Rheumatology.

According to Dr. Ranganathan, among 16,829 patients with RA, 3,096 were treated with anti-TNFs at the VA between Oct. 1, 1998, and Sept. 30, 2006. The incidence of nonmelanoma skin cancer was 25.9 per 1,000 patient-years in this cohort, compared with 19.6 per 1,000 patient-years in the biologic-naive cohort, a 34% increased risk.

The incidence of melanoma also was increased by about 50%, with about 3.7 cases per 1,000 patient-years seen in the anti-TNF-treated group, vs. 2.6 cases per 1,000 patient-years in the biologic-naive cohort. Both results were significant.

A second study presented at the press conference confirmed these findings. Dr. Kimme Hyrich of the University of Manchester (England) looked at RA patients from the British Society for Rheumatology's biologics register, a prospective cohort study begun in 2001 to monitor the long-term safety of anti-TNFs.

Dr. Hyrich found that among 11,598 RA patients who were treated with anti-TNFs and had no prior nonmelanoma skin cancer, the incidence of a malignancy was 3.5 per 1,000 patient-years. In contrast, among 8,975 similar patients who were treated with nonbiologic therapies, the incidence of new nonmelanoma skin cancers was 2.4.

That was a 70% increased risk for the anti-TNF–treated patients, although the data were not significant, Dr. Hyrich reported.

Dr. Hyrich pointed out that patients treated with anti-TNF drugs typically have more contact with their physicians, which could have introduced a surveillance bias.

Dr. Ranganathan cautioned that even in patients with multiple skin cancer risks anti-TNFs are still a good choice for patients who've failed other treatments. “People with risk factors should be watched more closely and maybe have periodic skin exams,” she said.

Dr. Ranganathan, Dr. Hyrich, and their respective research teams did not report having any financial conflicts relative to their studies.

Significantly more lupus patients responded to belimumab than placebo in a randomized trial with more than 800 patients followed for a year, the second positive outcome from a pivotal trial of the investigational monoclonal antibody in lupus this year.

After successfully meeting the primary end point in two large, separate lupus-treatment trials, Human Genome Sciences and GlaxoSmithKline, the two companies jointly developing belimumab (Benlysta), plan to file a new drug application with the Food and Drug Administration during the first half of 2010, said H. Thomas Watkins, president of HGS, during a conference call for investors.

If approved, it would be the first drug to receive a labeled indication for lupus in more than 50 years. Belimumab acts by blunting B-cell activity.

Initial results for the more recent of the two pivotal trials, the Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-76 study, were announced by HGS and GlaxoSmithKline in a press release, with a full report of the findings expected next summer. Initial results from the first pivotal trial, BLISS-52, were first released last July.

The primary outcome benefit from belimumab treatment was “solid,” said Dr. Joan T. Merrill, a specialist in treating systemic lupus erythematosus (SLE) who was a co-investigator on BLISS-76.

“The lupus community has waited decades for one positive phase III trial of an investigational drug developed for lupus. Now we have two.” Belimumab “may emerge as a significant new treatment for lupus,” said Dr. Merrill, professor of medicine at the University of Oklahoma Health Sciences Center in Oklahoma City. Dr. Merrill has served as a consultant to and has received research funding from HGS and GlaxoSmithKline as well as from several other drug companies.

BLISS-76 randomized 819 patients at 136 sites in 19 countries in North America and Europe. Enrollment criteria were not released for this study, but the similarly designed BLISS-52 trial included SLE patients with a score of 6 or more on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA SLEDAI). Patients also had to be seropositive for at least either antinuclear antibody at a level of 1:80 or greater or for anti–double stranded DNA at a level of 30 IU/mL or greater.

Patients were randomized to 1 mg/kg intravenous belimumab, 10 mg/kg intravenous belimumab, or placebo. Treatment occurred on days 0, 14, 28, and then every subsequent 28 days for 1 year. The study's primary end point was the percent of patients meeting the SLE Responder Index (SRI) after 52 weeks of treatment.

In BLISS-76 the SRI end point was reached by 43% of patients on the 10 mg/kg dosage, 41% of patients receiving 1 mg/kg, and 34% of patients on placebo. The difference in the outcome rate was statistically significant between the 10-mg/kg arm and placebo, but not between the 1-mg/kg arm and placebo. In BLISS-52, the rate of SRI responses at 52 weeks was 58% with the 10-mg/kg regimen compared with 44% in patients on placebo, also a statistically significant difference. The 10-mg/kg dosage is the one that HGS will pursue in its FDA filing, company officials said.

The safety profile of belimumab looked good in this study, as it had in BLISS-52, with no significant difference in the rates of malignancies, deaths, infections, serious infections, total adverse events, or serious adverse events among the treatment groups.

Significantly more lupus patients responded to belimumab than placebo in a randomized trial with more than 800 patients followed for a year, the second positive outcome from a pivotal trial of the investigational monoclonal antibody in lupus this year.

After successfully meeting the primary end point in two large, separate lupus-treatment trials, Human Genome Sciences and GlaxoSmithKline, the two companies jointly developing belimumab (Benlysta), plan to file a new drug application with the Food and Drug Administration during the first half of 2010, said H. Thomas Watkins, president of HGS, during a conference call for investors.

If approved, it would be the first drug to receive a labeled indication for lupus in more than 50 years. Belimumab acts by blunting B-cell activity.

Initial results for the more recent of the two pivotal trials, the Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-76 study, were announced by HGS and GlaxoSmithKline in a press release, with a full report of the findings expected next summer. Initial results from the first pivotal trial, BLISS-52, were first released last July.

The primary outcome benefit from belimumab treatment was “solid,” said Dr. Joan T. Merrill, a specialist in treating systemic lupus erythematosus (SLE) who was a co-investigator on BLISS-76.

“The lupus community has waited decades for one positive phase III trial of an investigational drug developed for lupus. Now we have two.” Belimumab “may emerge as a significant new treatment for lupus,” said Dr. Merrill, professor of medicine at the University of Oklahoma Health Sciences Center in Oklahoma City. Dr. Merrill has served as a consultant to and has received research funding from HGS and GlaxoSmithKline as well as from several other drug companies.

BLISS-76 randomized 819 patients at 136 sites in 19 countries in North America and Europe. Enrollment criteria were not released for this study, but the similarly designed BLISS-52 trial included SLE patients with a score of 6 or more on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA SLEDAI). Patients also had to be seropositive for at least either antinuclear antibody at a level of 1:80 or greater or for anti–double stranded DNA at a level of 30 IU/mL or greater.

Patients were randomized to 1 mg/kg intravenous belimumab, 10 mg/kg intravenous belimumab, or placebo. Treatment occurred on days 0, 14, 28, and then every subsequent 28 days for 1 year. The study's primary end point was the percent of patients meeting the SLE Responder Index (SRI) after 52 weeks of treatment.

In BLISS-76 the SRI end point was reached by 43% of patients on the 10 mg/kg dosage, 41% of patients receiving 1 mg/kg, and 34% of patients on placebo. The difference in the outcome rate was statistically significant between the 10-mg/kg arm and placebo, but not between the 1-mg/kg arm and placebo. In BLISS-52, the rate of SRI responses at 52 weeks was 58% with the 10-mg/kg regimen compared with 44% in patients on placebo, also a statistically significant difference. The 10-mg/kg dosage is the one that HGS will pursue in its FDA filing, company officials said.

The safety profile of belimumab looked good in this study, as it had in BLISS-52, with no significant difference in the rates of malignancies, deaths, infections, serious infections, total adverse events, or serious adverse events among the treatment groups.

Significantly more lupus patients responded to belimumab than placebo in a randomized trial with more than 800 patients followed for a year, the second positive outcome from a pivotal trial of the investigational monoclonal antibody in lupus this year.

After successfully meeting the primary end point in two large, separate lupus-treatment trials, Human Genome Sciences and GlaxoSmithKline, the two companies jointly developing belimumab (Benlysta), plan to file a new drug application with the Food and Drug Administration during the first half of 2010, said H. Thomas Watkins, president of HGS, during a conference call for investors.

If approved, it would be the first drug to receive a labeled indication for lupus in more than 50 years. Belimumab acts by blunting B-cell activity.

Initial results for the more recent of the two pivotal trials, the Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-76 study, were announced by HGS and GlaxoSmithKline in a press release, with a full report of the findings expected next summer. Initial results from the first pivotal trial, BLISS-52, were first released last July.

The primary outcome benefit from belimumab treatment was “solid,” said Dr. Joan T. Merrill, a specialist in treating systemic lupus erythematosus (SLE) who was a co-investigator on BLISS-76.

“The lupus community has waited decades for one positive phase III trial of an investigational drug developed for lupus. Now we have two.” Belimumab “may emerge as a significant new treatment for lupus,” said Dr. Merrill, professor of medicine at the University of Oklahoma Health Sciences Center in Oklahoma City. Dr. Merrill has served as a consultant to and has received research funding from HGS and GlaxoSmithKline as well as from several other drug companies.

BLISS-76 randomized 819 patients at 136 sites in 19 countries in North America and Europe. Enrollment criteria were not released for this study, but the similarly designed BLISS-52 trial included SLE patients with a score of 6 or more on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA SLEDAI). Patients also had to be seropositive for at least either antinuclear antibody at a level of 1:80 or greater or for anti–double stranded DNA at a level of 30 IU/mL or greater.

Patients were randomized to 1 mg/kg intravenous belimumab, 10 mg/kg intravenous belimumab, or placebo. Treatment occurred on days 0, 14, 28, and then every subsequent 28 days for 1 year. The study's primary end point was the percent of patients meeting the SLE Responder Index (SRI) after 52 weeks of treatment.

In BLISS-76 the SRI end point was reached by 43% of patients on the 10 mg/kg dosage, 41% of patients receiving 1 mg/kg, and 34% of patients on placebo. The difference in the outcome rate was statistically significant between the 10-mg/kg arm and placebo, but not between the 1-mg/kg arm and placebo. In BLISS-52, the rate of SRI responses at 52 weeks was 58% with the 10-mg/kg regimen compared with 44% in patients on placebo, also a statistically significant difference. The 10-mg/kg dosage is the one that HGS will pursue in its FDA filing, company officials said.

The safety profile of belimumab looked good in this study, as it had in BLISS-52, with no significant difference in the rates of malignancies, deaths, infections, serious infections, total adverse events, or serious adverse events among the treatment groups.

BERLIN — Psoriasis patients who show less than a PASI-50 response to 20 mg/wk of methotrexate by week 12 are unlikely to benefit from dosage increases or longer therapy, according to a new analysis of the CHAMPION study.

Week 12 has been found to be a useful decision point for discontinuing methotrexate and moving on to a biologic agent, said Dr. Jean-Hilaire Saurat, professor of dermatology at the University of Geneva.

“With the data we've obtained with CHAMPION, our understanding of how the treatment should be conducted should be reconsidered. We know that probably by week 12 we should know if the patient will respond or not,” said Dr. Saurat.

CHAMPION (Comparative Study of Adalimumab vs. Methotrexate vs. Placebo in Patients With Psoriasis) was a phase III, 16-week, double-blind, randomized trial in patients with moderate to severe psoriasis (Br. J. Dermatol. 2008;158:558–66).

The study provides the only existent placebo-controlled methotrexate data, noted Dr. Suarat, who presented the post hoc subanalysis results at the annual congress of the European Academy of Dermatology and Venereology.

CHAMPION included 103 evaluable patients randomized to 7.5 mg of oral methotrexate once weekly for 2 weeks, 10 mg weekly for the next 2 weeks, and then 15 mg/wk for 4 weeks.

The 40 patients with at least a PASI-50 response after 8 weeks—that is, a 50% reduction from baseline in Psoriasis Area and Severity Index scores—were deemed early responders. They remained on methotrexate 15 mg/wk for the rest of the 16-week study.

Patients with less than a PASI-50 at week 8 had their dosage increased to 20 mg/wk for 4 weeks. If at week 12 they had achieved a PASI-50 response they stayed on 20 mg/wk for the final 4 weeks of the study; if not, their dosage was increased to 25 mg/wk.

The 22 participants who reached PASI-50 after 8 weeks at dosages greater than 15 mg were classified as late responders; the 41 who never attained PASI-50 were deemed late nonresponders.

The mean weekly methotrexate dosage at 16 weeks was 14.5 mg in early responders, 19.5 mg in late responders, and 23.2 mg in late nonresponders. After 16 weeks, 27% of subjects had a PASI-75 response on a maximum dose of 15 mg/wk.

“The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab [Humira]. There is a group of patients on methotrexate who are extremely happy, and you do not need high doses to reach this response,” Dr. Saurat said.

The new findings from CHAMPION will be particularly useful for European physicians because psoriasis patients who require systemic therapy have to be treated with methotrexate before biologics can be considered, he suggested.

Audience member Dr. Craig L. Leonardi pointed out that methotrexate is still widely prescribed in the United States as well.

“I use methotrexate a lot these days. I've got hundreds of patients on it…. There's clearly a group of patients who do very well with this drug at low doses. It would be spectacular if we could predict which ones,” said Dr. Leonardi of the department of dermatology at Saint Louis University.

Unfortunately, Dr. Saurat said, no baseline predictors of early response in CHAMPION could be identified. Of note, however, patients destined for early responder status at week 8 already had a mean 40% reduction in PASI scores after just 4 weeks on methotrexate at 15 mg/wk.

The CHAMPION trial was sponsored by Abbott, which manufactures adalimumab. Dr. Saurat is an adviser to the company. Dr. Leonardi has served as a consultant to manufacturers of biologic agents for psoriasis.

'The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab.'

Source Dr. Saurat

'There's clearly a group of patients who do very well with this drug [methotrexate] at low doses.'

Source Dr. Leonardi

Source Elsevier Global Medical News

BERLIN — Psoriasis patients who show less than a PASI-50 response to 20 mg/wk of methotrexate by week 12 are unlikely to benefit from dosage increases or longer therapy, according to a new analysis of the CHAMPION study.

Week 12 has been found to be a useful decision point for discontinuing methotrexate and moving on to a biologic agent, said Dr. Jean-Hilaire Saurat, professor of dermatology at the University of Geneva.

“With the data we've obtained with CHAMPION, our understanding of how the treatment should be conducted should be reconsidered. We know that probably by week 12 we should know if the patient will respond or not,” said Dr. Saurat.

CHAMPION (Comparative Study of Adalimumab vs. Methotrexate vs. Placebo in Patients With Psoriasis) was a phase III, 16-week, double-blind, randomized trial in patients with moderate to severe psoriasis (Br. J. Dermatol. 2008;158:558–66).

The study provides the only existent placebo-controlled methotrexate data, noted Dr. Suarat, who presented the post hoc subanalysis results at the annual congress of the European Academy of Dermatology and Venereology.

CHAMPION included 103 evaluable patients randomized to 7.5 mg of oral methotrexate once weekly for 2 weeks, 10 mg weekly for the next 2 weeks, and then 15 mg/wk for 4 weeks.

The 40 patients with at least a PASI-50 response after 8 weeks—that is, a 50% reduction from baseline in Psoriasis Area and Severity Index scores—were deemed early responders. They remained on methotrexate 15 mg/wk for the rest of the 16-week study.

Patients with less than a PASI-50 at week 8 had their dosage increased to 20 mg/wk for 4 weeks. If at week 12 they had achieved a PASI-50 response they stayed on 20 mg/wk for the final 4 weeks of the study; if not, their dosage was increased to 25 mg/wk.

The 22 participants who reached PASI-50 after 8 weeks at dosages greater than 15 mg were classified as late responders; the 41 who never attained PASI-50 were deemed late nonresponders.

The mean weekly methotrexate dosage at 16 weeks was 14.5 mg in early responders, 19.5 mg in late responders, and 23.2 mg in late nonresponders. After 16 weeks, 27% of subjects had a PASI-75 response on a maximum dose of 15 mg/wk.

“The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab [Humira]. There is a group of patients on methotrexate who are extremely happy, and you do not need high doses to reach this response,” Dr. Saurat said.

The new findings from CHAMPION will be particularly useful for European physicians because psoriasis patients who require systemic therapy have to be treated with methotrexate before biologics can be considered, he suggested.

Audience member Dr. Craig L. Leonardi pointed out that methotrexate is still widely prescribed in the United States as well.

“I use methotrexate a lot these days. I've got hundreds of patients on it…. There's clearly a group of patients who do very well with this drug at low doses. It would be spectacular if we could predict which ones,” said Dr. Leonardi of the department of dermatology at Saint Louis University.

Unfortunately, Dr. Saurat said, no baseline predictors of early response in CHAMPION could be identified. Of note, however, patients destined for early responder status at week 8 already had a mean 40% reduction in PASI scores after just 4 weeks on methotrexate at 15 mg/wk.

The CHAMPION trial was sponsored by Abbott, which manufactures adalimumab. Dr. Saurat is an adviser to the company. Dr. Leonardi has served as a consultant to manufacturers of biologic agents for psoriasis.

'The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab.'

Source Dr. Saurat

'There's clearly a group of patients who do very well with this drug [methotrexate] at low doses.'

Source Dr. Leonardi

Source Elsevier Global Medical News

BERLIN — Psoriasis patients who show less than a PASI-50 response to 20 mg/wk of methotrexate by week 12 are unlikely to benefit from dosage increases or longer therapy, according to a new analysis of the CHAMPION study.

Week 12 has been found to be a useful decision point for discontinuing methotrexate and moving on to a biologic agent, said Dr. Jean-Hilaire Saurat, professor of dermatology at the University of Geneva.

“With the data we've obtained with CHAMPION, our understanding of how the treatment should be conducted should be reconsidered. We know that probably by week 12 we should know if the patient will respond or not,” said Dr. Saurat.

CHAMPION (Comparative Study of Adalimumab vs. Methotrexate vs. Placebo in Patients With Psoriasis) was a phase III, 16-week, double-blind, randomized trial in patients with moderate to severe psoriasis (Br. J. Dermatol. 2008;158:558–66).

The study provides the only existent placebo-controlled methotrexate data, noted Dr. Suarat, who presented the post hoc subanalysis results at the annual congress of the European Academy of Dermatology and Venereology.

CHAMPION included 103 evaluable patients randomized to 7.5 mg of oral methotrexate once weekly for 2 weeks, 10 mg weekly for the next 2 weeks, and then 15 mg/wk for 4 weeks.

The 40 patients with at least a PASI-50 response after 8 weeks—that is, a 50% reduction from baseline in Psoriasis Area and Severity Index scores—were deemed early responders. They remained on methotrexate 15 mg/wk for the rest of the 16-week study.

Patients with less than a PASI-50 at week 8 had their dosage increased to 20 mg/wk for 4 weeks. If at week 12 they had achieved a PASI-50 response they stayed on 20 mg/wk for the final 4 weeks of the study; if not, their dosage was increased to 25 mg/wk.

The 22 participants who reached PASI-50 after 8 weeks at dosages greater than 15 mg were classified as late responders; the 41 who never attained PASI-50 were deemed late nonresponders.

The mean weekly methotrexate dosage at 16 weeks was 14.5 mg in early responders, 19.5 mg in late responders, and 23.2 mg in late nonresponders. After 16 weeks, 27% of subjects had a PASI-75 response on a maximum dose of 15 mg/wk.

“The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab [Humira]. There is a group of patients on methotrexate who are extremely happy, and you do not need high doses to reach this response,” Dr. Saurat said.

The new findings from CHAMPION will be particularly useful for European physicians because psoriasis patients who require systemic therapy have to be treated with methotrexate before biologics can be considered, he suggested.

Audience member Dr. Craig L. Leonardi pointed out that methotrexate is still widely prescribed in the United States as well.

“I use methotrexate a lot these days. I've got hundreds of patients on it…. There's clearly a group of patients who do very well with this drug at low doses. It would be spectacular if we could predict which ones,” said Dr. Leonardi of the department of dermatology at Saint Louis University.

Unfortunately, Dr. Saurat said, no baseline predictors of early response in CHAMPION could be identified. Of note, however, patients destined for early responder status at week 8 already had a mean 40% reduction in PASI scores after just 4 weeks on methotrexate at 15 mg/wk.

The CHAMPION trial was sponsored by Abbott, which manufactures adalimumab. Dr. Saurat is an adviser to the company. Dr. Leonardi has served as a consultant to manufacturers of biologic agents for psoriasis.

'The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab.'

Source Dr. Saurat

'There's clearly a group of patients who do very well with this drug [methotrexate] at low doses.'

Source Dr. Leonardi

Source Elsevier Global Medical News